NF-κB-Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis.

PubMed

Rodrigues, Paulo; Patel, Saroor A; Harewood, Louise; Olan, Ioana; Vojtasova, Erika; Syafruddin, Saiful E; Zaini, M Nazhif; Richardson, Emma K; Burge, Johanna; Warren, Anne Y; Stewart, Grant D; Saeb-Parsy, Kourosh; Samarajiwa, Shamith A; Vanharanta, Sakari

2018-06-06

Metastases, the spread of cancer cells to distant organs, cause the majority of cancer-related deaths. Few metastasis-specific driver mutations have been identified, suggesting aberrant gene regulation as a source of metastatic traits. However, how metastatic gene expression programs arise is poorly understood. Here, using human-derived metastasis models of renal cancer, we identify transcriptional enhancers that promote metastatic carcinoma progression. Specific enhancers and enhancer clusters are activated in metastatic cancer cell populations, and the associated gene expression patterns are predictive of poor patient outcome in clinical samples. We find that the renal cancer metastasis-associated enhancer complement consists of multiple coactivated tissue-specific enhancer modules. Specifically, we identify and functionally characterize a coregulatory enhancer cluster, activated by the renal cancer driver HIF2A and an NF-κB-driven lymphoid element, as a mediator of metastasis in vivo We conclude that oncogenic pathways can acquire metastatic phenotypes through cross-lineage co-option of physiologic epigenetic enhancer states. SIGNIFICANCE: Renal cancer is associated with significant mortality due to metastasis. We show that in metastatic renal cancer, functionally important metastasis genes are activated via co-option of gene regulatory enhancer modules from distant developmental lineages, thus providing clues to the origins of metastatic cancer. Cancer Discov; 8(7); 1-16. ©2018 AACR. ©2018 American Association for Cancer Research.

Dehydration upon admission is a risk factor for incomplete recovery of renal function in children with haemolytic uremic syndrome.

PubMed

Ojeda, José M; Kohout, Isolda; Cuestas, Eduardo

2013-01-01

Haemolytic uremic syndrome (HUS) is the most common cause of acute renal failure and the second leading cause of chronic renal failure in children. The factors that affect incomplete renal function recovery prior to hospital admission are poorly understood. To analyse the risk factors that determine incomplete recovery of renal function prior to hospitalisation in children with HUS. A retrospective case-control study. age, sex, duration of diarrhoea, bloody stools, vomiting, fever, dehydration, previous use of antibiotics, and incomplete recovery of renal function (proteinuria, hypertension, reduced creatinine clearance, and chronic renal failure during follow-up). Patients of both sexes under 15 years of age were included. Of 36 patients, 23 were males (65.3%; 95%CI: 45.8 to 80.9), with an average age of 2.5 ± 1.4 years. Twenty-one patients required dialysis (58%; 95% CI: 40.8 to 75.8), and 13 (36.1%; 95% CI: 19.0 to 53.1) did not recover renal function. In the bivariate model, the only significant risk factor was dehydration (defined as weight loss >5%) [(OR: 5.3; 95% CI: 1.4 to 12.3; P=.0220]. In the multivariate analysis (Cox multiple regression), only dehydration was marginally significant (HR: 95.823; 95% CI: 93.175 to 109.948; P=.085). Our data suggest that dehydration prior to admission may be a factor that increases the risk of incomplete recovery of renal function during long-term follow-up in children who develop HUS D+. Consequently, in patients with diarrhoea who are at risk of HUS, dehydration should be strongly avoided during outpatient care to preserve long-term renal function. These results must be confirmed by larger prospective studies.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

PubMed Central

Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C.; Khadayate, Sanjay; Mas, Valeria R.; Nitsch, Dorothea D.; Wang, Zhen; Norman, Jill T.; Wilcox, Christopher S.; Wheeler, David C.; Leiper, James

2015-01-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. PMID:25855779

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction

PubMed Central

2013-01-01

Background Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Methods Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Results Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. Conclusion These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction. PMID:23849513

Changes in leucocyte migration after renal transplantation

PubMed Central

Smith, M. G. M.; Eddleston, A. L. W. F.; Dominguez, J. A.; Evans, D. B.; Bewick, M.; Williams, Roger

1969-01-01

The leucocyte migration test, an in-vitro measure of cellular immunity, has been used to follow the changes in cell-mediated hypersensitivity to kidney and histocompatibility antigens in three patients after renal transplantation. Inhibition of leucocyte migration, indicating strong sensitization to the antigens used, occurred in each patient, starting five to seven days after transplantation. Satisfactory renal function had not been established in any of the patients at this time. In one case inhibition of leucocyte migration persisted almost continuously until the 24th day and was associated with poor renal function proved histologically to be due to rejection. Treatment with increased dosage of prednisone was associated with a rapid reversion to normal of the migration index and improvement in renal function. Later, inhibition of migration occurred again, and shortly afterwards the graft ceased to function. In the other two cases the migration index became normal without alteration in immunosuppressive therapy and a satisfactory diuresis followed. It is suggested that this simple test should prove useful in the specific diagnosis of rejection and in control of immunosuppressive therapy. ImagesFig. 3Fig. 4 PMID:4899455

Functional renal imaging: new trends in radiology and nuclear medicine.

PubMed

Durand, Emmanuel; Chaumet-Riffaud, Philippe; Grenier, Nicolas

2011-01-01

The objective of this work is to compare the characteristics of various techniques for functional renal imaging, with a focus on nuclear medicine and magnetic resonance imaging. Even with low spatial resolution and rather poor signal-to-noise ratio, classical nuclear medicine has the advantage of linearity and good sensitivity. It remains the gold standard technique for renal relative functional assessment. Technetium-99m ((99m)Tc)-labeled diethylenetriamine penta-acetate remains the reference glomerular tracer. Tubular tracers have been improved: (123)I- or (131)I-hippuran, (99m)Tc-MAG3 and, recently, (99m)Tc-nitrilotriacetic acid. However, advancement in molecular imaging has not produced a groundbreaking tracer. Renal magnetic resonance imaging with classical gadolinated tracers probably has potential in this domain but has a lack of linearity and, therefore, its value still needs evaluation. Moreover, the advent of nephrogenic systemic fibrosis has delayed its expansion. Other developments, such as diffusion or blood oxygen level-dependent imaging, may have a role in the future. The other modalities have a limited role in clinical practice for functional renal imaging. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of renal function status on the prognostic value of heart rate in acute ischemic stroke patients.

PubMed

Zhu, Zhengbao; Zhong, Chongke; Xu, Tian; Wang, Aili; Peng, Yanbo; Xu, Tan; Peng, Hao; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Geng, Deqin; Sun, Yingxian; Du, Qingjuan; Li, Yongqiu; Chen, Jing; Zhang, Yonghong; He, Jiang

2017-08-01

The association between heart rate and prognosis of ischemic stroke remains debatable, and whether renal function status influences the relationship between them is still not elucidated. A total of 3923 ischemic stroke patients were included in this prospective multicenter study from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes were, separately, death and major disability. The association between heart rate tertiles and primary outcome was appreciably modified by renal function status (p interaction  = 0.037). After multivariate adjustment, high heart rate was associated with increased risk of primary outcome in patients with abnormal renal function (odds ratio, 1.61; 95% confidence interval, 1.02-2.54; p trend  = 0.039) but not in patients with normal renal function (odds ratio, 0.96; 95% confidence interval, 0.75-1.23; p trend  = 0.741), when two extreme tertiles were compared. Each 10 bpm increase of heart rate was associated with 21% (95% CI: 1%-44%) increased risk of primary outcome, and a linear association between heart rate and risk of primary outcome was observed among patients with abnormal renal function (p for linearity = 0.002). High heart rate may be merely a strong predictor of poor prognosis in acute ischemic stroke patients with abnormal renal function, suggesting that heart rate reduction should be applied to ischemic stroke patients with abnormal renal function to improve their prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Significance of Anti-Ribosomal P Protein Antibodies in Patients with Lupus Nephritis.

PubMed

Sarfaraz, Sabahat; Anis, Sabiha; Ahmed, Ejaz; Muzaffar, Rana

2018-04-09

Systemic lupus erythematosus (SLE) is achronic inflammatory disorder affecting multiplesystems of the body. Clinical features show wide variations in patients with different ethnic background. Renal involvement is a predictor of poor prognosis. Immunological workup is an integral part of SLE diagnostic criteria. Anti-ribosomal P Protein (anti-P) antibodies are highly specific for SLE. They may be present inantinuclear antibodies (ANA) negative SLE patients. Their role in lupus nephritis (LN) is under debate, some researchers found them associated with poor prognosiswhereasothers found favorable effect of these antibodies on renal disease. In this study we investigated frequency of anti-P antibodies and the effect of these antibodies on renal functions in LN patients. A total of 133SLE patientswere enrolled in this study. All patients had ANA in their sera. Anti-P antibodies along with other autoantibodiesagainstextractable nuclearantigens (anti-Sm, anti-SS-A, anti-SS-B, anti-histones and anti-RNP) were detected by Immunoblot assay. Anti-dsDNA antibodies were detected by indirect immunofluorescence assay (IFA). We found anti-P antibodies in 10.5% LN patients. Interestingly their presence in association with anti-dsDNA was associated with improved renal functions in comparison to those who had anti-dsDNA antibodies in isolation (serum creatinine: 1.3 ± 0.8 mg/dl vs. 3.0 ± 3.0; P= 0.091). Anti-dsDNA antibodies are directly involved in renal pathology in SLE patients. As these antibodies are nephrotoxic, concomitant occurrence of anti-P antibodies seems to offer a shielding effect on renal functions, which was evident by normal serum creatinine levels. Therefore anti-P antibodies may be considered as a good prognostic marker in these patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage.

PubMed

Tomlinson, James A P; Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C; Khadayate, Sanjay; Mas, Valeria R; Nitsch, Dorothea D; Wang, Zhen; Norman, Jill T; Wilcox, Christopher S; Wheeler, David C; Leiper, James

2015-12-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule-specific Ddah1 knockout (Ddah1(PT-/-)) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1(PT-/-) mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. Copyright © 2015 by the American Society of Nephrology.

Sleep disorders in kidney disease.

PubMed

De Santo, R M; Perna, A; Di Iorio, B R; Cirillo, M

2010-03-01

Sleep disorders are common in patients with end stage renal disease receiving hemodialysis or peritoneal dialysis. However also a well functioning renal graft does not cure the poor sleep pattern which now emerges as a problem even in early chronic kidney disease (CKD). When patients are made aware for the first time of a disease such as CKD, which may brink to dialysis or at the best to a renal transplant patients begin to experience a disordered sleep. Sleeping disorders include insomnia (I), sleep apnoea (SAS), restless legs syndrome (RLS), periodic limb movement disorder (PLMD), excessive daily sleeping (EDS), sleepwalking, nightmares, and narcolepsy. Disordered sleep did not meet the clinical and scientific interest it deserves, in addition and we do not have a well defined solution for sleeping complaints. However, awareness that a poor sleep is associated with poor quality of life and carries an increase in mortality risk has recently stimulated interest in the field. There are many putative causes for a disordered sleep in chronic kidney disease and in end-stage renal disease. For a unifying hypothesis demographic factors, lifestyles, disease related factors, psychological factors, treatment related factors, and social factor must be taken into consideration.

Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

PubMed

Liu, Xue-Jing; Wu, Xiao-Yue; Wang, Huan; Wang, Su-Xia; Kong, Wei; Zhang, Ling; Liu, George; Huang, Wei

2018-05-08

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue (AT) and could lead to renal failure in humans. However, the effect of Seipin on renal function is poorly understood. Here we report that Seipin knockout (SKO) mice exhibited impaired renal function, enlarged glomerular and mesangial surface areas, renal depositions of lipid, and advanced glycation end products. Elevated glycosuria and increased electrolyte excretion were also detected. Relative renal gene expression in fatty acid oxidation and reabsorption pathways were impaired in SKO mice. Elevated glycosuria might be associated with reduced renal glucose transporter 2 levels. To improve renal function, AT transplantation or leptin administration alone was performed. Both treatments effectively ameliorated renal injury by improving all of the parameters that were measured in the kidney. The treatments also rescued insulin resistance and low plasma leptin levels in SKO mice. Our findings demonstrate for the first time that Seipin deficiency induces renal injury, which is closely related to glucolipotoxicity and impaired renal reabsorption in SKO mice, and is primarily caused by the loss of AT and especially the lack of leptin. AT transplantation and leptin administration are two effective treatments for renal injury in Seipin-deficient mice.-Liu, X.-J., Wu, X.-Y., Wang, H., Wang, S.-X., Kong, W., Zhang, L., Liu, G., Huang, W. Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

Acute renal infarction: Clinical characteristics and prognostic factors.

PubMed

Caravaca-Fontán, Fernando; Pampa Saico, Saúl; Elías Triviño, Sandra; Galeano Álvarez, Cristina; Gomis Couto, Antonio; Pecharromán de las Heras, Inés; Liaño, Fernando

2016-01-01

Acute renal infarction (ARI) is an uncommon disease, whose real incidence is probably higher than expected. It is associated with poor prognosis in a high percentage of cases. To describe the main clinical, biochemical and radiologic features and to determine which factors are associated with poor prognosis (death or permanent renal injury). The following is a retrospective, observational, single-hospital-based study. All patients diagnosed with ARI by contrast-enhanced computed tomography (CT) over an 18-year period were included. Patients were classified according to the cardiac or non-cardiac origin of their disease. Clinical, biochemical and radiologic features were analysed, and multiple logistic regression model was used to determine factors associated with poor prognosis. A total of 62 patients were included, 30 of which had a cardiac origin. Other 32 patients with non-cardiac ARI were younger, had less comorbidity, and were less frequently treated with oral anticoagulants. CT scans estimated mean injury extension at 35%, with no differences observed between groups. A total of 38% of patients had an unfavourable outcome, and the main determinants were: Initial renal function (OR=0.949; IC 95% 0.918-0.980; p=0.002), and previous treatment with oral anticoagulants (OR=0.135; IC 95% 0.032-0.565; p=0.006). ARI is a rare pathology with non-specific symptoms, and it is not associated with cardiological disease or arrhythmias in more than half of cases. A substantial proportion of patients have unfavourable outcomes, and the initial renal function is one of the main prognostic factors. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Pulmonary Catherization Data Correlate Poorly with Renal Function in Heart Failure.

PubMed

Masha, Luke; Stone, James; Stone, Danielle; Zhang, Jun; Sheng, Luo

2018-04-10

The mechanisms of renal dysfunction in heart failure are poorly understood. We chose to explore the relationship of cardiac filling pressures and cardiac index (CI) in relation to renal dysfunction in advanced heart failure. To determine the relationship between renal function and cardiac filling pressures using the United Network of Organ Sharing (UNOS) pulmonary artery catherization registry. Patients over the age of 18 years who were listed for single-organ heart transplantation were included. Exclusion criteria included a history of mechanical circulatory support, previous transplantation, any use of renal replacement therapy, prior history of malignancy, and cardiac surgery, amongst others. Correlations between serum creatinine (SCr) and CI, pulmonary capillary wedge pressure (PCWP), pulmonary artery systolic pressure (PASP), and pulmonary artery diastolic pressure (PADP) were assessed by Pearson correlation coefficients and simple linear regression coefficients. Pearson correlation coefficients between SCr and PCWP, PASP, and PADP were near zero with values of 0.1, 0.07, and 0.08, respectively (p < 0.0001). A weak negative correlation coefficient between SCr and CI was found (correlation coefficient, -0.045, p = 0.027). In a subgroup of young patients unlikely to have noncardiac etiologies, no significant correlations between these values were identified. These findings suggest that, as assessed by pulmonary artery catherization, none of the factors - PCWP, PASP, PADP, or CI - play a prominent role in cardiorenal syndromes. © 2018 S. Karger AG, Basel.

Wound Healing in Patients With Impaired Kidney Function

PubMed Central

Maroz, Natallia; Simman, Richard

2014-01-01

Renal impairment has long been known to affect wound healing. However, information on differences in the spectrum of wound healing depending on the type of renal insufficiency is limited. Acute kidney injury (AKI) may be observed with different wound types. On one hand, it follows acute traumatic conditions such as crush injury, burns, and post-surgical wounds, and on the other hand, it arises as simultaneous targeting of skin and kidneys by autoimmune-mediated vasculitis. Chronic kidney disease (CKD) and end-stage renal disease (ESRD) often occur in older people, who have limited physical mobility and predisposition for developing pressure-related wounds. The common risk factors for poor wound healing, generally observed in patients with CKD and ESRD, include poorly controlled diabetes mellitus, neuropathy, peripheral vascular disease, chronic venous insufficiency, and aging. ESRD patients have a unique spectrum of wounds related to impaired calcium–phosphorus metabolism, including calciphylaxis, in addition to having the risk factors presented by CKD patients. Overall, there is a wide range of uremic toxins: they may affect local mechanisms of wound healing and also adversely affect the functioning of multiple systems. In the present literature review, we discuss the association between different types of renal impairments and their effects on wound healing and examine this association from different aspects related to the management of wounds in renal impairment patients. PMID:26199882

[Assisted peritoneal dialysis: home-based renal replacement therapy for the elderly patient].

PubMed

Wiesholzer, Martin

2013-06-01

The number of elderly patients with end stage renal disease is constantly increasing. Conventional hämodiaylsis as the mainstay of renal replacement therapy is often poorly tolerated by frail eldery patients with multiple comorbidities. Although many of these patients would prefer a home based dialysis treatment, the number of elderly patients using peritoneal dialysis (PD) is still low. Impaired physical and cognitive function often generates insurmountable barriers for self care peritoneal dialysis. Assisted peritoneal dialysis can overcome many of these barriers and give elderly patients the ability of a renal replacement therapy in their own homes respecting their needs.

Renal angioplasty and stenting: is it still indicated after ASTRAL and STAR studies?

PubMed

Henry, M; Benjelloun, A; Henry, I; Polydorou, A; Hugel, M

2010-10-01

A renal artery stenosis (RAS) is common among patients with atherosclerosis, up to a third of patients undergoing cardiac catheterization. Fibromuscular dysplasia is the next cause of RAS, commonly found in young women. Atherosclerosis RAS generally progresses overtime and is often associated with loss of renal mass and worsening renal function (RF). Percutaneous renal artery stent placement is the preferred method of revascularization for hemodynamically significant RAS according to ACC and AHA guidelines. Several randomized trials have shown the superiority of endovascular procedures to medical therapy alone. However, two studies ASTRAL and STAR studies were recently published and did not find any difference between renal stenting and medical therapy. But these studies have a lot of limitations and flaws as we will discuss (poor indications, poor results, numerous complications, failures, poor technique, inexperienced operators, ecc.). Despite these questionable studies, renal stenting keeps indications in patients with: uncontrolled hypertension; ischemic nephropathy; cardiac disturbance syndrome (e.g. "flash" pulmonary edema, uncontrolled heart failure or uncontrolled angina pectoris); solitary kidney. To improve the clinical response rates, a better selection of the patients and lesions is mandatory with: good non-invasive or invasive imaging; physiologic lesion assessment using transluminal pressure gradients; measurements of biomarkers (e.g., BNP); fractional flow reserve study. A problem remains after renal angioplasty stenting, the deterioration of the RF in 20-30% of the patients. Atheroembolism seems to play an important role and is probably the main cause of this R.F deterioration. The use of protection devices alone or in combination with IIb IIa inhibitors has been proposed and seems promising as shown in different recent reports. Renal angioplasty and stenting is still indicated but we need: a better patient and lesion selection; improvements in techniques and maybe the use of protection devices to reduce the risk of RF deterioration after renal stenting.

Hepatitis A complicated with acute renal failure and high hepatocyte growth factor: A case report.

PubMed

Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

2015-08-28

A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.

Renal Safety Pharmacology in Drug Discovery and Development.

PubMed

Benjamin, Amanda; Nogueira da Costa, Andre; Delaunois, Annie; Rosseels, Marie-Luce; Valentin, Jean-Pierre

2015-01-01

The kidney is a complex excretory organ playing a crucial role in various physiological processes such as fluid and electrolyte balance, control of blood pressure, removal of waste products, and drug disposition. Drug-induced kidney injury (DIKI) remains a significant cause of candidate drug attrition during drug development. However, the incidence of renal toxicities in preclinical studies is low, and the mechanisms by which drugs induce kidney injury are still poorly understood. Although some in vitro investigational tools have been developed, the in vivo assessment of renal function remains the most widely used methodology to identify DIKI. Stand-alone safety pharmacology studies usually include assessment of glomerular and hemodynamic function, coupled with urine and plasma analyses. However, as renal function is not part of the ICH S7A core battery, such studies are not routinely conducted by pharmaceutical companies. The most common approach consists in integrating renal/urinary measurements in repeat-dose toxicity studies. In addition to the standard analyses and histopathological examination of kidneys, novel promising urinary biomarkers have emerged over the last decade, offering greater sensitivity and specificity than traditional renal parameters. Seven of these biomarkers have been qualified by regulatory agencies for use in rat toxicity studies.

Volumetric Nephrogram Represents Renal Function and Complements Aortic Anatomic Severity Grade in Predicting EVAR Outcomes.

PubMed

Balceniuk, Mark D; Trakimas, Lauren; Aghaie, Claudia; Mix, Doran; Rasheed, Khurram; Seaman, Matthew; Ellis, Jennifer; Glocker, Roan; Doyle, Adam; Stoner, Michael C

2018-07-01

Chronic kidney disease (CKD) is a predictor of poor outcomes for patients undergoing endovascular aortic aneurysm repair (EVAR). Anatomic severity grade (ASG) represents a quantitative mechanism for assessing anatomical suitability for endovascular aortic repair. Anatomic severity grade has been correlated with repair outcomes and resource utilization. The purpose of this study was to identify a novel renal perfusion metric as a way to assist ASG with predicting EVAR outcomes. Retrospective review of a prospectively maintained database identified elective infrarenal aortic aneurysm repair cases. Anatomic grading was undertaken by independent reviewers. Using volumetric software, kidney volume, and a novel measure of kidney functional volume, the volumetric nephrogram (VN) was recorded. Systematic evaluation of the relationship of kidney volume and VN to CKD and ASG was undertaken using linear regression and receiver-operator statistical tools. A total of 386 cases with patient and anatomic data were identified and graded. Mean age was 72.9 ± 0.4 years. Renal volume <281 mL correlated with CKD (area under the curve [AUC] = .708; P ≤ .0001). Volumetric nephrogram <22.5 HU·L correlated with CKD (AUC = 0.764; P ≤ .0001). High (≥15) ASG scores correlated with both renal volume (AUC = .628; P ≤ .0001) and VN (AUC = .628; P ≤ .0001). Regression analysis demonstrated a strong, inverse relationship between ASG and VN ( R 2 = .95). These data demonstrate that VN is a strong predictor of CKD in a large database of patients undergoing elective aneurysm repair. We demonstrate an inverse relationship between renal function and ASG that has not been previously described in the literature. Additionally, we have shown that VN complements ASG as a model of overall cardiovascular health and atherosclerotic burden. Outcomes in patients with poor renal function may be related to anatomical issues in addition to well-described systemic ramifications.

Intensity ratio curve analysis of small renal masses on T2-weighted magnetic resonance imaging: Differentiation of fat-poor angiomyolipoma from renal cell carcinoma.

PubMed

Moriyama, Shingo; Yoshida, Soichiro; Tanaka, Hajime; Tanaka, Hiroshi; Yokoyama, Minato; Ishioka, Junichiro; Matsuoka, Yoh; Saito, Kazutaka; Kihara, Kazunori; Fujii, Yasuhisa

2018-03-25

To assess the diagnostic ability of a pixel intensity-based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat-poor angiomyolipoma from renal cell carcinoma. T2-weighted images from 121 solid small renal masses (<4 cm) without visible fat (14 fat-poor angiomyolipomas, 92 clear cell renal cell carcinomas, six chromophobe renal cell carcinomas and nine papillary renal cell carcinomas) were retrospectively evaluated. An intensity ratio curve was plotted using intensity ratios, which were ratios of signal intensities of tumor pixels (each pixel along a linear region of interest drawn across the renal tumor on T2-weighted image) to the signal intensity of a normal renal cortex. The diagnostic ability of the intensity ratio curve analysis was evaluated. The tumors were classified into three types: intensity ratio fat-poor angiomyolipoma (n = 19) with no pseudocapsule, iso-low intensity and no heterogeneity; intensity ratio clear cell renal cell carcinoma (n = 76) with a pseudocapsule, iso-high intensity and heterogeneity; and other type of intensity ratio (n = 26), including tumors that did not fall into the above two categories. The sensitivity/specificity/accuracy of the intensity ratio curve analysis in diagnosing fat-poor angiomyolipoma was 93%/94%/94%, respectively. When the intensity ratio curve analysis was applied only to the tumor with undetermined radiological diagnosis, the sensitivity for diagnosing fat-poor angiomyolipoma compared with subjective reading alone significantly improved (93% vs 50%; P = 0.014). Our novel semiquantitative model for combined assessment of key features of fat-poor angiomyolipoma, including low intensity, homogeneity and absence of a pseudocapsule on T2-weighted image, might make diagnosis of fat-poor angiomyolipoma more accurate. © 2018 The Japanese Urological Association.

Quality of sleep and health-related quality of life in renal transplant recipients.

PubMed

Liu, Hong-Xia; Lin, Jun; Lin, Xiao-Hong; Wallace, Linda; Teng, Sha; Zhang, Shu-Ping; Hao, Yu-Fang

2015-01-01

The purpose of this study was to examine the sleep quality and health-related quality of life (HRQOL) in patients after renal transplantation and to explore the relationship between the quality of sleep and the HRQOL. Sleep disorders are still an important clinical problem after renal transplantation. Previous studies mainly focused on patients' sleep quality before kidney transplant. More studies are needed to document sleep quality after renal transplantation. A cross-sectional design was used in this study. A convenience sample of renal transplant recipients was recruited at an outpatient transplant clinic of a general hospital in Beijing, China. The Pittsburgh Sleep Quality Index (PSQI) was used to measure quality of sleep. The Medical Outcomes Study 36-item Short Form (MOS SF-36) was used to measure health-related quality of life. The average PSQI score of the 204 renal transplant recipients was 5.81±3.52, significantly lower than the norm. Fifty (24.5%) recipients were classified as having poor sleep quality (global PSQI > 7). The mean scores of renal transplant recipients for SF-36 Mental Component Summary (MCS) and Physical Component Summary (PCS) were 47.57±6.71 and 48.26±9.66 respectively. Compared with residents in Sichuan province, recipients' scores for SF-36 dimensions were statistically lower except the dimension of mental health. SF-36 scores of poor sleepers (PSQI > 7) were significantly lower than the good sleepers (PSQI ≤ 7) in both the MCS and PCS. Significant differences exist between the groups in physical function, bodily pain, vitality, and mental health dimensions. Sleep quality and HRQOL of patients after renal transplantation were lower than the norm. Poor sleep is associated with lower HRQOL. Health professionals need to pay attention to sleep quality and HRQOL in renal transplant recipients and take appropriate measures to improve patients' sleep quality and HRQOL.

Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China

PubMed Central

Qin, Dan-dan; Wu, Li-hua; Song, Yan; Yu, Feng; Wang, Su-xia; Liu, Gang; Zhao, Ming-hui

2015-01-01

Objective The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features. Design A retrospective cohort study. Participants Seventy-nine patients with renal biopsy-proven lupus nephritis, diagnosed between January 2000 and June 2008 from Peking University First Hospital. Results In clinico-pathological data, patients with arteriosclerosis had higher ratio of hypertension and more severe renal injury indices compared with patients with no renal vascular lesions. More importantly, patients with renal arteriosclerosis had worse cardiac structure and function under transthoracic echocardiographic examination. Patients with renal arteriosclerosis tend to have higher ratios of combined endpoints compared with those of no renal vascular lesions, although the difference didn’t reach statistical meanings (P = 0.104). Conclusion Renal arteriosclerotic lesion was common and associated with vascular immune complex deposits in lupus nephritis. It might have a certain degree of association with poor outcomes and cardiovascular events, which needs further explorations. PMID:26544865

The renal concentrating mechanism and the clinical consequences of its loss

PubMed Central

Agaba, Emmanuel I.; Rohrscheib, Mark; Tzamaloukas, Antonios H.

2012-01-01

The integrity of the renal concentrating mechanism is maintained by the anatomical and functional arrangements of the renal transport mechanisms for solute (sodium, potassium, urea, etc) and water and by the function of the regulatory hormone for renal concentration, vasopressin. The discovery of aquaporins (water channels) in the cell membranes of the renal tubular epithelial cells has elucidated the mechanisms of renal actions of vasopressin. Loss of the concentrating mechanism results in uncontrolled polyuria with low urine osmolality and, if the patient is unable to consume (appropriately) large volumes of water, hypernatremia with dire neurological consequences. Loss of concentrating mechanism can be the consequence of defective secretion of vasopressin from the posterior pituitary gland (congenital or acquired central diabetes insipidus) or poor response of the target organ to vasopressin (congenital or nephrogenic diabetes insipidus). The differentiation between the three major states producing polyuria with low urine osmolality (central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia) is done by a standardized water deprivation test. Proper diagnosis is essential for the management, which differs between these three conditions. PMID:23293407

Endourological treatment of nonmalignant upper urinary tract complications after urinary diversion.

PubMed

El-Nahas, Ahmed R; Shokeir, Ahmed A

2010-12-01

Endourological modalities are considered the first line of treatment for benign ureterointestinal anastomotic strictures except in long strictures, completely obliterated lumen, prior radiation, and poor renal function. Endoureterotomy provided better success than balloon dilatation. In poor-operative risk patients, metal or double-J stents are viable options. Endourological treatments of upper tract stones after diversion are indicated for stones not suitable for shock wave lithotripsy (SWL) or to salvage SWL failure. Percutaneous nephrolithotomy was preferred for large or complex renal stones, whereas ureteroscopy was used for smaller stones. The evaluation of stone-free status and regular follow-up are mandatory because of the high recurrence rate. Copyright © 2010 Elsevier Inc. All rights reserved.

Extracorporeal Ultrafiltration for Fluid Overload in Heart Failure

PubMed Central

Costanzo, Maria Rosa; Ronco, Claudio; Abraham, William T.; Agostoni, Piergiuseppe; Barasch, Jonathan; Fonarow, Gregg C.; Gottlieb, Stephen S.; Jaski, Brian E.; Kazory, Amir; Levin, Allison P.; Levin, Howard R.; Marenzi, Giancarlo; Mullens, Wilfried; Negoianu, Dan; Redfield, Margaret M.; Tang, W.H. Wilson; Testani, Jeffrey M.; Voors, Adriaan A.

2017-01-01

More than 1 million heart failure hospitalizations occur annually, and congestion is the predominant cause. Rehospitalizations for recurrent congestion portend poor outcomes independently of age and renal function. Persistent congestion trumps serum creatinine increases in predicting adverse heart failure outcomes. No decongestive pharmacological therapy has reduced these harmful consequences. Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital settings, but with conflicting results regarding safety and efficacy. Ultrafiltration performed at fixed rates after onset of therapy-induced increased serum creatinine was not superior to standard care and resulted in more complications. In contrast, compared with diuretic agents, some data suggest that adjustment of ultrafiltration rates to patients’ vital signs and renal function may be associated with more effective decongestion and fewer heart failure events. Essential aspects of ultrafiltration remain poorly defined. Further research is urgently needed, given the burden of congestion and data suggesting sustained benefits of early and adjustable ultrafiltration. PMID:28494980

Diuretic 99mTc DTPA renography in assessment of renal function and drainage in infants with antenatally detected hydronephrosis.

PubMed

Radulović, Marija; Pucar, Dragan; Jauković, Ljiljana; Sisić, Marija; Krstić, Zoran; Ajdinović, Boris

2015-12-01

The controversy over the postnatal management of infants with antenataly detected hydronephrosis (ANH) still exists. We presented the results of diuretic 99mTc diethylenetriamine pentaacetic acid (DTPA) renography in 30 infants with the antenatal diagnosis of unilateral renal pelvic dilatation. The aim of this study was to assess the renal function determined by the pattern of drainage and split renal function (SRF) on diuretic renography and to correlate these findings with anteroposterior pelvic diameter (APD) estimated by ultrasonography. A total of 30 infants with 60 renal units (RU) (25 boys and 5 girls, median age 6.0 months, range 2-24) presented with unilateral hydronephrosis on ultrasound in the newborn period, underwent DTPA diuretic renal scintigraphy (F+15 protocol). The median APD evaluated on perinatal ultrasound was 15 mm (range 5-30). The postnatal associated clinical diagnosis were pelviureteric junction obstruction (PUJ), simple hydronephrosis, megaureter, vesicoureteral reflux (VUR) and posterior urethral valves in 11, 10, 6, 2 and 1 infant, respectively. Images and Tmax/2 after diuretic stimulation on the background subtracted renographic curves were used as the criteria for classifying the drainage as good, partial, and poor or no drainage. The SRF was calculated with the integral method. Good drainage was shown in 36/60, partial drainage in 13/60 and poor or no drainage in 11/60 RU. The SRF > 40% was observed in 55/60 RU, with no RU showing SRF lower than 23.5%. In infants with severe ANH the obstruction was not excluded in 94.1%. Diuretic renography in antenatally detected hydronephrosis should be a useful tool in postnatal follow up, especially in differentiating nonobstructive hydronephrosis from obstructive. It is also importanat to assess and monitor the SRF. Our results suggest that even in the presence of partial or no drainage, SRF may not be significantly impaired.

[Renal failure in patients with liver transplant: incidence and predisposing factors].

PubMed

Gerona, S; Laudano, O; Macías, S; San Román, E; Galdame, O; Torres, O; Sorkin, E; Ciardullo, M; de Santibañes, E; Mastai, R

1997-01-01

Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The aim of the present study was to evaluate the incidence, prognostic value of pre, intra and postoperative factors and severity of renal dysfunction in patients who undergo liver transplantation. Therefore, the records of 38 consecutive adult patients were reviewed. Renal failure was defined arbitrarily as an increase in creatinine (> 1.5 mg/dl) and/or blood urea (> 80 mg/dl). Three patients were excluded of the final analysis (1 acute liver failure and 2 with a survival lower than 72 hs.) Twenty one of the 35 patients has renal failure after orthotopic liver transplantation. Six of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 15 patients within the hospitalization (40 +/- 10 days) (Mean +/- SD). In he overall series, liver function, evaluated by Child-Pugh classification, a higher blood-related requirements and cyclosporine levels were observed more in those who experienced renal failure than those who did not (p < 0.05). Early renal failure was related with preoperative (liver function) and intraoperative (blood requirements) factors and several causes (nephrotoxic drugs and graft failure) other than cyclosporine were present in patients who developed late renal impairment. No mortality. No mortality was associated with renal failure. We conclude that renal failure a) is a common finding after liver transplantation, b) the pathogenesis of this complication is multifactorial and, c) in not related with a poor outcome.

Prediction of cardiovascular outcome by estimated glomerular filtration rate and estimated creatinine clearance in the high-risk hypertension population of the VALUE trial.

PubMed

Ruilope, Luis M; Zanchetti, Alberto; Julius, Stevo; McInnes, Gordon T; Segura, Julian; Stolt, Pelle; Hua, Tsushung A; Weber, Michael A; Jamerson, Ken

2007-07-01

Reduced renal function is predictive of poor cardiovascular outcomes but the predictive value of different measures of renal function is uncertain. We compared the value of estimated creatinine clearance, using the Cockcroft-Gault formula, with that of estimated glomerular filtration rate (GFR), using the Modification of Diet in Renal Disease (MDRD) formula, as predictors of cardiovascular outcome in 15 245 high-risk hypertensive participants in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. For the primary end-point, the three secondary end-points and for all-cause death, outcomes were compared for individuals with baseline estimated creatinine clearance and estimated GFR < 60 ml/min and > or = 60 ml/min using hazard ratios and 95% confidence intervals. Coronary heart disease, left ventricular hypertrophy, age, sex and treatment effects were included as covariates in the model. For each end-point considered, the risk in individuals with poor renal function at baseline was greater than in those with better renal function. Estimated creatinine clearance (Cockcroft-Gault) was significantly predictive only of all-cause death [hazard ratio = 1.223, 95% confidence interval (CI) = 1.076-1.390; P = 0.0021] whereas estimated GFR was predictive of all outcomes except stroke. Hazard ratios (95% CIs) for estimated GFR were: primary cardiac end-point, 1.497 (1.332-1.682), P < 0.0001; myocardial infarction, 1.501 (1.254-1.796), P < 0.0001; congestive heart failure, 1.699 (1.435-2.013), P < 0.0001; stroke, 1.152 (0.952-1.394) P = 0.1452; and all-cause death, 1.231 (1.098-1.380), P = 0.0004. These results indicate that estimated glomerular filtration rate calculated with the MDRD formula is more informative than estimated creatinine clearance (Cockcroft-Gault) in the prediction of cardiovascular outcomes.

Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

PubMed Central

Iacoviello, Massimo; Leone, Marta; Antoncecchi, Valeria; Ciccone, Marco Matteo

2015-01-01

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure (CHF) which are independently associated with poor patient outcome. The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index (a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction. PMID:25610846

Changes in renal function after implantation of continuous-flow left ventricular assist devices.

PubMed

Hasin, Tal; Topilsky, Yan; Schirger, John A; Li, Zhuo; Zhao, Yanjun; Boilson, Barry A; Clavell, Alfredo L; Rodeheffer, Richard J; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Joyce, Lyle; Daly, Richard; Park, Soon J; Kushwaha, Sudhir S

2012-01-03

The aim of this study was to determine renal outcomes after left ventricular assist device (LVAD) implantation. Renal dysfunction before LVAD placement is frequent, and it is unclear whether it is due to primary renal disease or to poor perfusion. A retrospective single-center analysis was conducted in 83 consecutive patients implanted with HeartMate II continuous-flow LVADs (Thoratec Corp., Pleasanton, California). Calculated glomerular filtration rate (GFR) was assessed on admission and 1, 3, and 6 months after implantation. To define predictors for improvement in GFR, clinical variables were examined in patients with decreased renal function (GFR <60 ml/min/1.73 m(2)) before LVAD, surviving and dialysis-free at 1 month (n = 44). GFR significantly increased from admission (53.2 ± 21.4 ml/min/1.73 m(2)) to 1 month after LVAD implantation (87.4 ± 27.9 ml/min/1.73 m(2)) (p < 0.0001). Subsequently, at 3 and 6 months, GFR remained significantly (p < 0.0001) above pre-LVAD values. Of the 51 patients with GFRs <60 ml/min/1.73 m(2) before LVAD surviving at 1 month, 34 (67%) improved to GFRs >60 ml/min/1.73 m(2). Univariate pre-operative predictors for improvement in renal function at 1 month included younger age (p = 0.049), GFR improvement with optimal medical therapy (p < 0.001), intra-aortic balloon pump use (p = 0.004), kidney length above 10 cm (p = 0.023), no treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (p = 0.029), higher bilirubin (p = 0.002), higher Lietz-Miller score (p = 0.019), and atrial fibrillation (p = 0.007). Multivariate analysis indicated pre-operative improved GFR (slope = 0.5 U per unit improved; 95% confidence interval: 0.2 to 0.8; p = 0.003), atrial fibrillation (slope = 27; 95% confidence interval: 8 to 46; p = 0.006), and intra-aortic balloon pump use (slope = 14; 95% confidence interval: 2 to 26; p = 0.02) as independent predictors. In most patients with end-stage heart failure considered for LVAD implantation, renal dysfunction is reversible and likely related to poor renal perfusion. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The impact of slow graft function on graft outcome is comparable to delayed graft function in deceased donor kidney transplantation.

PubMed

Shin, Jung-Ho; Koo, Eun Hee; Ha, Sung Hae; Park, Ji Hyeon; Jang, Hye Ryoun; Lee, Jung Eun; Park, Jae-Berm; Kim, Sung Joo; Jung, Sin-Ho; Kim, Yoon-Goo; Kim, Dae Joong; Oh, Ha Young; Huh, Wooseong

2016-03-01

Slow graft function (SGF) can influence overall prognosis in patients receiving deceased donor kidney transplantation (DKT). However, the impact of SGF on renal function remains uncertain. We investigated retrospectively renal function in cases with SGF compared with early graft function (EGF) and delayed graft function (DGF). Renal function after transplantation was analyzed in 199 patients who underwent DKT. Patients were classified into 130 (65.3 %) cases with EGF, 27 (13.6 %) cases with SGF, 6 (3.0 %) cases with DGF and one dialysis (DGF1), and 36 (18.1 %) cases with DGF and two or more dialyses (DGF2). The 1-year estimated glomerular filtration rate (eGFR) in the SGF group was lower than that in the EGF group (P = 0.027), but the rate of eGFR decline did not differ between the groups. The risk factors for renal function were evaluated using the area under the eGFR curve over 3 years (AUCeGFR). Donor age was negatively, and recipient age and the number of HLA matches were positively correlated with the AUCeGFR (all P < 0.05). A multivariate analysis revealed that the AUCeGFR was lower in cases of younger recipient age, older donor age, and acute rejection (all P < 0.05). The AUCeGFR was significantly lower in the SGF and DGF2 groups compared with the EGF group (P = 0.031 and 0.006, respectively). SGF may be an independent risk factor for poor renal function after DKT. Moreover, it was comparable to DGF. Efforts should be dedicated to minimizing the development of SGF and DGF.

Hepatorenal syndrome.

PubMed

Papper, S

1980-01-01

Renal failure without apparent cause (the hepatorenal syndrome) may develop in the course of cirrhosis of the liver. While the development of renal failure bears a poor prognosis, spontaneous recovery can occur. The data suggest that for the most part patients die in rather than of renal failure. The latter seems to be only part of a broader more fundamental disturbance. The pathogenesis of HRS is unknown, but the evidence supports an impairment of effective renal perfusion. The two major hypotheses concerning the nature of the impaired perfusion are that it is a physiologic response to alterations in the extrarenal circulation, and that there is an unidentified humoral agent(s) produced by or inadequately inactivated by or bypassing the diseased liver and causing circulatory changes in the kidney as well as in other organs. It is possible that both mechanisms are operative. Treatment is unsatisfactory and emphasis is presently best placed upon searching for more treatable causes of renal functional impairment in individual patients.

[Clinical case of acute renal failure revealing an autoimmune hypothyroidism].

PubMed

Montasser, Dina Ibrahim; Hassani, Mohamed; Zajjari, Yassir; Bahadi, Abdelali; Alayoud, Ahmed; Hamzi, Amine; Hassani, Kawtar; Moujoud, Omar; Asseraji, Mohamed; Kadiri, Moncif; Aatif, Taoufik; El Kabbaj, Driss; Benyahia, Mohamed; Allam, Mustapha; Akhmouch, Ismail; Oualim, Zouhir

2010-04-01

Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a wide range of metabolic disturbances. Hypothyroidism is associated with significant effects on the kidney which the pathophysiology seems to be multifactorial, but the exact mechanisms remain poorly understood. Hypothyroidism as a cause of renal impairment is usually overlooked, leading to unnecessary diagnostic procedures. The main objective of our observation is to report a case of acute renal failure revealing an autoimmune hypothyroidism in which thyroid hormone substitution led to a significant improvement in muscular, thyroid and renal disorders. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Pregnancy and renal outcomes in lupus nephritis: an update and guide to management.

PubMed

Bramham, K; Soh, M C; Nelson-Piercy, C

2012-10-01

Systemic lupus erythematosis (SLE) commonly affects women of child bearing-age, and advances in treatment have resulted in an increasing number of women with renal involvement becoming pregnant. Knowledge of the relationship of the condition with respect to fertility and pregnancy is important for all clinicians involved in the care of women with lupus nephritis because they have complicated pregnancies. Presentation of lupus nephritis can range from mild asymptomatic proteinuria to rapidly progressive renal failure and may occur before, during, or after pregnancy. The timing of diagnosis may influence pregnancy outcome. Pregnancy may also affect the course of lupus nephritis. All pregnancies in women with lupus nephritis should be planned, preferably after more than six-months of quiescent disease. Predictors of poor obstetric outcome include active disease at conception or early pregnancy, baseline poor renal function with Creatinine >100 μmol/L, proteinuria >0.5 g/24 hours, presence of concurrent antiphospholipid syndrome and hypertension. In this review the most recent studies of pregnancies in women with lupus nephritis are discussed and a practical approach to managing women prepregnancy, during pregnancy and post-partum is described.

Effect of renal impairment on the pharmacokinetics of exenatide

PubMed Central

Linnebjerg, Helle; Kothare, Prajakti A; Park, Soomin; Mace, Kenneth; Reddy, Shobha; Mitchell, Malcolm; Lins, Robert

2007-01-01

What is already known about this subject Nonclinical studies have shown that exenatide is primarily cleared by the renal system. It was not known to what degree the clinical pharmacokinetics and tolerability would be affected by increasing renal impairment (RI). What this study adds Patients with mild to moderate RI adequately tolerate current therapeutic doses of exenatide.However, exenatide is not recommended in patients with severe RI or end-stage renal disease. Aims To evaluate the pharmacokinetics (PK), safety and tolerability of a single exenatide dose in patients with renal impairment (RI). Methods Exenatide (5 or 10 µg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function [Cockcroft–Gault creatinine clearance (CrCL), number of subjects]: normal (>80 ml min−1, n = 8), mild RI (51–80 ml min−1, n = 8), moderate RI (31–50 ml min−1, n = 7) or end-stage renal disease (ESRD) requiring haemodialysis (n = 8). PK data were combined with four previous single-dose studies in patients with Type 2 diabetes to explore the relationship of exenatide clearance (CLp/F) and CrCL. Results Mean half-life for healthy, mild RI, moderate RI and ESRD groups were 1.5, 2.1, 3.2 and 6.0 h, respectively. After combining data from multiple studies, least squares geometric means for CLp/F in subjects with normal renal function, mild RI, moderate RI and ESRD were 8.14, 5.19, 7.11 and 1.3 l h−1, respectively. Exenatide was generally well tolerated in the mild and moderate RI groups, but not in subjects with ESRD due to nausea and vomiting. Simulations of exenatide plasma concentrations also suggest patients with ESRD should have a propensity for poor tolerability at the lowest available therapeutic dosage (5 µg q.d.). Conclusions Since tolerability and PK changes were considered clinically acceptable in patients with mild to moderate RI, it would be appropriate to administer exenatide to these patients without dosage adjustment. However, poor tolerability and significant changes in PK make the currently available therapeutic doses (5 and 10 µg) unsuitable in severe RI or ESRD. PMID:17425627

Accuracy of cystatin C for the detection of abnormal renal function in children undergoing chemotherapy for malignancy: a systematic review using individual patient data.

PubMed

Whiting, Penny; Birnie, Kate; Sterne, Jonathan A C; Jameson, Catherine; Skinner, Rod; Phillips, Bob

2018-05-01

We conducted a systematic review and individual patient data (IPD) meta-analysis to examine the utility of cystatin C for evaluation of glomerular function in children with cancer. Eligible studies evaluated the accuracy of cystatin C for detecting poor renal function in children undergoing chemotherapy. Study quality was assessed using QUADAS-2. Authors of four studies shared IPD. We calculated the correlation between log cystatin C and GFR stratified by study and measure of cystatin C. We dichotomized the reference standard at GFR 80 ml/min/1.73m 2 and stratified cystatin C at 1 mg/l, to calculate sensitivity and specificity in each study and according to age group (0-4, 5-12, and ≥ 13 years). In sensitivity analyses, we investigated different GFR and cystatin C cut points. We used logistic regression to estimate the association of impaired renal function with log cystatin C and quantified diagnostic accuracy using the area under the ROC curve (AUC). Six studies, which used different test and reference standard thresholds, suggested that cystatin C has the potential to monitor renal function in children undergoing chemotherapy for malignancy. IPD data (504 samples, 209 children) showed that cystatin C has poor sensitivity (63%) and moderate specificity (89%), although use of a GFR cut point of < 60 ml/min/1.73m 2 (data only available from two of the studies) estimated sensitivity to be 92% and specificity 81.3%. The AUC for the combined data set was 0.890 (95% CI 0.826, 0.951). Diagnostic accuracy appeared to decrease with age. Cystatin C has better diagnostic accuracy than creatinine as a test for glomerular dysfunction in young people undergoing treatment for cancer. Diagnostic accuracy is not sufficient for it to replace current reference standards for predicting clinically relevant impairments that may alter dosing of important nephrotoxic agents.

[Managing focal incidental renal lesions].

PubMed

Nicolau, C; Paño, B; Sebastià, C

2016-01-01

Incidental renal lesions are relatively common in daily radiological practice. It is important to know the different diagnostic possibilities for incidentally detected lesions, depending on whether they are cystic or solid. The management of cystic lesions is guided by the Bosniak classification. In solid lesions, the goal is to differentiate between renal cancer and benign tumors such as fat-poor angiomyolipoma and oncocytoma. Radiologists need to know the recommendations for the management of these lesions and the usefulness of the different imaging techniques and interventional procedures in function of the characteristics of the incidental lesion and the patient's life expectancy. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Coexistence of Anti-Glomerular Basement Membrane Glomerulonephritis and Membranous Nephropathy in a Female Patient with Preserved Renal Function.

PubMed

Ogawara, Aoi; Harada, Makoto; Ichikawa, Tohru; Fujii, Kazuaki; Ehara, Takashi; Kobayashi, Mamoru

2017-12-01

Renal prognosis for anti-glomerular basement membrane (GBM) glomerulonephritis is poor. The greater the amount of anti-GBM antibody binding the antigen (type IV collagen of the glomerular basement membrane), the greater the number of crescents that develop in glomeruli, resulting in progression of renal impairment. Immunofluorescence staining reveals linear IgG depositions on glomerular capillary walls. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in middle-aged to elderly patients. Immune complex is deposited in the sub-epithelial space of the glomerulus resulting in the development of a membranous lesion. Immunofluorescence staining reveals granular IgG depositions on glomerular capillary walls. Coexisting anti-GBM glomerulonephritis and MN are rare and, here we report a case of coexisting anti-GBM glomerulonephritis and MN with preserved renal function. There are some cases of coexisting anti-GBM glomerulonephritis and MN do not show severely decreased renal function. A 76-year-old Japanese woman presented with nephrotic syndrome, microscopic hematuria, and was positive for anti-GBM antibody. Kidney biopsy revealed linear and granular IgG depositions in glomerular capillary walls, crescent formations, and electron-dense deposits in the sub-epithelial space. She was diagnosed with anti-GBM glomerulonephritis and MN. Steroid and cyclosporine therapy achieved complete remission, and kidney function was preserved. In conclusion, coexisting anti-GBM glomerulonephritis and MN can have preserved renal function. IgG subclass of deposited anti-GBM antibody may be associated with the severity of anti-GBM glomerulonephritis. In addition, in the case of nephrotic syndrome with hematuria, we should consider the possibility of coexisting anti-GBM glomerulonephritis and MN.

Serotonin levels in platelet-poor plasma and whole blood in people with type 2 diabetes with chronic kidney disease.

PubMed

Hara, Katsuko; Hirowatari, Yuji; Shimura, Yuko; Takahashi, Hakuo

2011-11-01

Patients with diabetes mellitus (DM) are prone to atherosclerosis. Atherosclerosis activates platelets; activated platelets release serotonin, and therefore, evaluation of serotonin levels in blood could be a valuable biomarker for future risk of cardiovascular events. Plasma serotonin levels obtained from patients with DM complicated with chronic kidney disease were measured using HPLC and were compared to serotonin levels of healthy control subjects. Patients with DM were classified into 2 subgroups of mildly (group 1) and moderately/severely (group 2) impaired renal function. Serotonin concentration in platelet-poor plasma for group 1 was significantly higher than that of healthy control subjects (p < 0.01), and was significantly higher than that of patients from group 2 (p < 0.05). The concentration of serotonin in whole blood for group 2 patients was significantly lower than that measured from healthy control subjects (p < 0.01). The ratio of the plasma to whole blood level was significantly elevated in both groups 1 and 2 compared with healthy controls (p < 0.01). Our results indicate that platelets are activated to release serotonin into plasma in diabetic patients with mildly impaired renal function. When renal damage is advanced, platelets are over-activated to release serotonin. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Renal arterial resistive index is associated with severe histological changes and poor renal outcome during chronic kidney disease

PubMed Central

2012-01-01

Background Chronic kidney disease (CKD) is a growing public health problem and end stage renal disease (ESRD) represents a large human and economic burden. It is important to identify patients at high risk of ESRD. In order to determine whether renal Doppler resistive index (RI) may discriminate those patients, we analyzed whether RI was associated with identified prognosis factors of CKD, in particular histological findings, and with renal outcome. Methods RI was measured in the 48 hours before renal biopsy in 58 CKD patients. Clinical and biological data were collected prospectively at inclusion. Arteriosclerosis, interstitial fibrosis and glomerulosclerosis were quantitatively assessed on renal biopsy in a blinded fashion. MDRD eGFR at 18 months was collected for 35 (60%) patients. Renal function decline was defined as a decrease in eGFR from baseline of at least 5 mL/min/ 1.73 m2/year or need for chronic renal replacement therapy. Pearson’s correlation, Mann–Whitney and Chi-square tests were used for analysis of quantitative and qualitative variables respectively. Kaplan Meier analysis was realized to determine renal survival according to RI value using the log-rank test. Multiple logistic regression was performed including variables with p < 0.20 in univariate analysis. Results Most patients had glomerulonephritis (82%). Median age was 46 years [21–87], eGFR 59 mL/min/ 1.73m2 [5–130], percentage of interstitial fibrosis 10% [0–90], glomerulosclerosis 13% [0–96] and RI 0.63 [0.31-1.00]. RI increased with age (r = 0.435, p = 0.0063), pulse pressure (r = 0.303, p = 0.022), renal atrophy (r = −0.275, p = 0.038) and renal dysfunction (r = −0.402, p = 0.0018). Patients with arterial intima/media ratio ≥ 1 (p = 0.032), interstitial fibrosis > 20% (p = 0.014) and renal function decline (p = 0.0023) had higher RI. Patients with baseline RI ≥ 0.65 had a poorer renal outcome than those with baseline RI < 0.65 (p = 0.0005). In multiple logistic regression, RI≥0.65 was associated with accelerated renal function decline independently of baseline eGFR and proteinuria/creatininuria ratio (OR=13.04 [1.984-85.727], p = 0.0075). Sensitivity, specificity, predictive positive and predictive negative values of RI ≥ 0.65 for renal function decline at 18 months were respectively 77%, 86%, 71% and 82%. Conclusions Our results suggest that RI ≥ 0.65 is associated with severe interstitial fibrosis and arteriosclerosis and renal function decline. Thus, RI may contribute to identify patients at high risk of ESRD who may benefit from nephroprotective treatments. PMID:23098365

The use of renal replacement therapy in acute decompensated heart failure.

PubMed

Udani, Suneel M; Murray, Patrick T

2009-01-01

The worsening of renal function in the context of decompensated heart failure is an increasingly common clinical scenario, dubbed the cardiorenal syndrome. Its development is not completely understood; however, it results from the hemodynamic and neurohumoral alterations that occur in the setting of left ventricular pressure and volume overload with poor cardiac output. Diuretics have been the mainstay of treatment; however, they are often unsuccessful in reversing the vicious cycle of volume overload, worsening cardiac function, and azotemia. Renal replacement therapy (RRT) in the form of isolated or continuous ultrafiltration (UF) with or without a component of solute clearance (hemofiltration or hemodialysis) has been increasingly utilized as a therapeutic tool in this setting. Initial clinical trial data on the use of UF have demonstrated promising cardiac outcomes with regard to fluid removal and symptom relief without worsening renal function. The addition of a component of solute clearance may provide additional benefits in these patients with varying degrees of renal impairment. The exact clinical setting in which the various forms of RRT should be applied as initial or early therapy for acute decompensated heart failure (ADHF) remains unknown. More research examining the use of RRT in ADHF is necessary; however, it appears that the patients with the most severe clinical presentations have the best chance of benefiting from the early application of RRT.

Maternal determinants of renal mass and function in the fetus and neonate.

PubMed

Brophy, Patrick

2017-04-01

The impact of adverse maternal and early gestational issues, ranging from maternal-fetal interactions all the way through to premature birth, are recognized as having influence on the subsequent development of chronic diseases later in life. The development of chronic kidney disease (CKD) as a direct result of early life renal injury or a sequela of diseases such as hypertension or diabetes is a good model example of the potential impact that early life events may have on renal development and lifelong function. The global monetary and human resource cost of CKD is exorbitant. Socio-economic factors, along with other factors (genetic and environmental) may significantly influence the timing and display of phenotypic expression in fetuses and neonates at risk for developing CKD, yet very few of these factors are studied or well understood. In general our focus has been directed at treatment once CKD is established. This strategy has been and remains short-sighted and costly. Earlier understanding of the intrauterine determinants of renal mass development (i.e. environmental "biomes", poor maternal-fetal health, socio-economic factors impacting early life events, diet, access to value based health care and educational opportunities on disease evolution) may allow us an opportunity for earlier intervention. This article aims to provide some foundation for improved understanding of the maternal determinants of renal mass and function in the fetus and neonate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Both in- and out-hospital worsening of renal function predict outcome in patients with heart failure: results from the Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH).

PubMed

Damman, Kevin; Jaarsma, Tiny; Voors, Adriaan A; Navis, Gerjan; Hillege, Hans L; van Veldhuisen, Dirk J

2009-09-01

The effect of worsening renal function (WRF) after discharge on outcome in patients with heart failure is unknown. We assessed estimated glomerular filtration rate (eGFR) and serum creatinine at admission, discharge, and 6 and 12 months after discharge, in 1023 heart failure patients. Worsening renal function was defined as an increase in serum creatinine of >26.5 micromol/L and >25%. The primary endpoint was a composite of all-cause mortality and heart failure admissions. The mean age of patients was 71 +/- 11 years, and 62% was male. Mean eGFR at admission was 55 +/- 21 mL/min/1.73 m(2). In-hospital WRF occurred in 11% of patients, while 16 and 9% experienced WRF from 0 to 6, and 6 to 12 months after discharge, respectively. In multivariate landmark analysis, WRF at any point in time was associated with a higher incidence of the primary endpoint: hazard ratio (HR) 1.63 (1.10-2.40), P = 0.014 for in-hospital WRF, HR 2.06 (1.13-3.74), P = 0.018 for WRF between 0-6 months, and HR 5.03 (2.13-11.88), P < 0.001 for WRF between 6-12 months. Both in- and out-hospital worsening of renal function are independently related to poor prognosis in patients with heart failure, suggesting that renal function in heart failure patients should be monitored long after discharge.

Localized renal cell carcinoma management: an update.

PubMed

Heldwein, Flavio L; McCullough, T Casey; Souto, Carlos A V; Galiano, Marc; Barret, Eric

2008-01-01

To review the current modalities of treatment for localized renal cell carcinoma. A literature search for keywords: renal cell carcinoma, radical nephrectomy, nephron sparing surgery, minimally invasive surgery, and cryoablation was performed for the years 2000 through 2008. The most relevant publications were examined. New epidemiologic data and current treatment of renal cancer were covered. Concerning the treatment of clinically localized disease, the literature supports the standardization of partial nephrectomy and laparoscopic approaches as therapeutic options with better functional results and oncologic success comparable to standard radical resection. Promising initial results are now available for minimally invasive therapies, such as cryotherapy and radiofrequency ablation. Active surveillance has been reported with acceptable results, including for those who are poor surgical candidates. This review covers current advances in radical and conservative treatments of localized kidney cancer. The current status of nephron-sparing surgery, ablative therapies, and active surveillance based on natural history has resulted in great progress in the management of localized renal cell carcinoma.

Functional genomic analysis identifies indoxyl sulfate as a major, poorly dialyzable uremic toxin in end-stage renal disease.

PubMed

Jhawar, Sachin; Singh, Prabhjot; Torres, Daniel; Ramirez-Valle, Francisco; Kassem, Hania; Banerjee, Trina; Dolgalev, Igor; Heguy, Adriana; Zavadil, Jiri; Lowenstein, Jerome

2015-01-01

Chronic renal failure is characterized by progressive renal scarring and accelerated arteriosclerotic cardiovascular disease despite what is considered to be adequate hemodialysis or peritoneal dialysis. In rodents with reduced renal mass, renal scarring has been attributed to poorly filtered, small protein-bound molecules. The best studied of these is indoxyl sulfate (IS). We have attempted to establish whether there are uremic toxins that are not effectively removed by hemodialysis. We examined plasma from patients undergoing hemodialysis, employing global gene expression in normal human renal cortical cells incubated in pre- and post- dialysis plasma as a reporter system. Responses in cells incubated with pre- and post-dialysis uremic plasma (n = 10) were compared with responses elicited by plasma from control subjects (n = 5). The effects of adding IS to control plasma and of adding probenecid to uremic plasma were examined. Plasma concentrations of IS were measured by HPLC (high pressure liquid chromatography). Gene expression in our reporter system revealed dysregulation of 1912 genes in cells incubated with pre-dialysis uremic plasma. In cells incubated in post-dialysis plasma, the expression of 537 of those genes returned to baseline but the majority of them (1375) remained dysregulated. IS concentration was markedly elevated in pre- and post-dialysis plasma. Addition of IS to control plasma simulated more than 80% of the effects of uremic plasma on gene expression; the addition of probenecid, an organic anion transport (OAT) inhibitor, to uremic plasma reversed the changes in gene expression. These findings provide evidence that hemodialysis fails to effectively clear one or more solutes that effect gene expression, in our reporter system, from the plasma of patients with uremia. The finding that gene dysregulation was simulated by the addition of IS to control plasma and inhibited by addition of an OAT inhibitor to uremic plasma identifies IS as a major, poorly dialyzable, uremic toxin. The signaling pathways initiated by IS and possibly other solutes not effectively removed by dialysis may participate in the pathogenesis of renal scarring and uremic vasculopathy.

[Change of creatinine clearance rate in accordance with aging in Japanese patients with head and neck cancer].

PubMed

Nishimura, Goshi; Horiuchi, Choichi; Yoshida, Takafumi; Kawakami, Mariko; Yabuki, Kenichiro; Taguchi, Takahide; Nagao, Junichi; Kondo, Norio; Masuda, Yoko; Matsuda, Hideki; Mikami, Yasukazu; Tsukuda, Mamoru

2006-04-01

Most of the head and neck tumors are squamous cell carcinomas (SCCs), which are relatively sensitive to chemotherapeutic agents. Cis-platinum (CDDP), 5-fluorouracil and taxanes are widely used worldwide for SCCs, and CDDP is the most common agent. Renal toxicity is a well-known adverse effect of CDDP, and adequate pre and post-hydration or combined administration of neutralizing agents is performed during CDDP injection. Before the CDDP administration, we have to evaluate renal function of the patients using creatinine clearance rate (Ccr). In Japan, CDDP at the dose of 60-70 mg/m(2)/day is administered in cases with over 65 ml/min/1.73 m(2) of Ccr, whereas in cases under 60 ml/min/1.73 m(2), we use other drugs, e.g., carboplatin, to prevent the renal dysfunction followed by chemotherapy. In other countries, the dose of CDDP is 70-100 mg/m(2)/day, and the discrepancy is based on the poor renal function of Japanese. We calculated Ccrs of 107 head and neck cancer patients since January, 2004 to August, 2005, and evaluated renal function before any treatment. Ccr was decreased in proportion to aging. At the age of fifties, 43.5% of the patients indicated lower Ccr than 65 ml/min/1.73 m(2): sixties, 45.7%; seventies, 50.0%; and eighties, 85.7%. In the United States, the average glomerular filtration rate of over 70 year-old healthy people is estimated as 75 ml/min/ 1.73 m(2), and it is considered sufficient kidney function for the administration of CDDP at the dose of 70-100 mg/ m(2)/day. The incident rate of end-stage renal disease is 1.3 times higher in the United States than in Japan. The incident rate of diabetes, which is the main cause of renal dysfunction, is almost the same in both countries. Though the reason is unclear, it is the fact that the renal function of Japanese decreases quickly in accordance with aging.

Impaired renal function is associated with worse self-reported outcomes after kidney transplantation.

PubMed

Neri, Luca; Dukes, Jonathan; Brennan, Daniel C; Salvalaggio, Paulo R; Seelam, Susmitha; Desiraju, Srividya; Schnitzler, Mark

2011-12-01

We sought to determine the association between health-related quality of life (HRQOL) and graft function in renal transplant recipients. We enrolled 577 kidney transplant recipients aged 18-74 years (response rate 87%). Recipients with multiple or multi-organ transplantation, creatine kinase >200 U/L, acute renal failure or cellular rejection (n = 64), and without creatinine assessments in 3 months pre-enrollment (n = 127) were excluded. The questionnaire included Euro QOL 5 Dimensions (EQ-5D), Health Utility Index III (HUI-III), Kidney Disease Quality of Life-36 (KDQOL36) which include a generic section (RAND SF-12). Data on medical conditions, therapy regimens, and biochemistry results were extracted from clinical charts. We used general linear models adjusted for demographic, socioeconomic, and clinical characteristics to assess the association between HRQOL and severity of chronic kidney disease (CKD). Patients with more advanced CKD were more likely to be African-American, covered by public insurance, more likely to have shorter time after transplantation, higher phosphorus and lower hemoglobin, serum albumin, and calcium levels. All HRQOL scales were inversely associated with CKD severity. All associations were robust to adjustment for possible confounders. Several health-related quality of life dimensions may be affected by poor renal function after transplantation.

Erythrocyte deformation in ischemic acute tubular necrosis and amelioration by splenectomy in the dog.

PubMed

Mandal, A K; Taylor, C A; Bell, R D; Hillman, N M; Jarnot, M D; Cunningham, J D; Phillips, L G

1991-11-01

Bilateral renal artery occlusion (RAO) for 120 minutes in dogs results in acute tubular necrosis (ATN) and peritubular capillary (PTC) congestion with rapidly deteriorating renal function. We have shown that prior splenectomy minimizes RAO-induced renal functional and histopathologic changes. The purpose of this study was to examine whether this renal protection is due to prevention of red blood cell echinocyte formation and resultant renal PTC congestion. Echinocytes (burr cells) are poorly deformable, impart high viscosity to the blood, and may hinder reperfusion by increasing resistance to renal capillary blood flow. Splenectomized (SPLX) or sham-SPLX dogs were treated with bilateral RAO for 120 minutes. After RAO, renal function and renal blood flow were monitored, and peripheral blood red blood cells were examined at 1 hour and at 24-hour intervals for 96 hours. Renal biopsies were taken 1 hour after RAO and the kidneys removed 96 hours after RAO. The RBCs and renal tissues were studied using scanning electron microscopy. Renal function was assessed by endogenous creatinine clearance. Sham-SPLX animals showed a marked and sustained decrease in creatinine clearance, consistently elevated serum creatinine levels and fractional excretion of sodium, and diffuse ATN and PTC congestion with echinocytes. These animals had a peak in circulating echinocytes 1 hour after RAO (p less than 0.05), which showed an excellent negative correlation with creatinine clearance (r = -0.999; p less than 0.001). On the contrary, SPLX animals had essentially no change in serum creatinine or fractional excretion of sodium, minimal tubular changes, no PTC congestion, and no rise in circulating echinocytes during the 96-hour observation. In vitro treatment of the postischemic red blood cells from sham animals with adenosine-inosine or fresh postischemic plasma from the SPLX animals showed almost complete reversal to discocytes (normal red blood cells), whereas in vitro treatment of postischemic red blood cells from the SPLX animals with fresh postischemic plasma from the sham animals resulted in a marked echinocytic response. We conclude that 1) a marked echinocyte response in the immediate postischemic period is an important mechanism in initiating ischemic ATN, 2) an echinocyte inducing factor may reside in the plasma of spleen-intact animals, and 3) mitigation of ATN and PTC congestion by splenectomy is, at least in part, consequential to attenuated echinocytic response in the immediate postischemic period.

Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin

PubMed Central

Liu, Qingdu; Binns, Thomas C.; Davidoff, Olena; Kapitsinou, Pinelopi P.; Pfaff, Andrew S.; Olauson, Hannes; Fogo, Agnes B.; Fong, Guo-Hua; Gross, Kenneth W.

2016-01-01

Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2–/– renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2–/– mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801

Long non-coding RNA GAS5 sensitizes renal cell carcinoma to sorafenib via miR-21/SOX5 pathway.

PubMed

Liu, Lei; Pang, Xinlu; Shang, Wenjin; Xie, Hongchang; Feng, Yonghua; Feng, Guiwen

2018-06-12

Although the use of sorafenib appears to increase the survival rate of renal cell carcinoma (RCC) patients, there is also a proportion of patients who exhibit a poor primary response to sorafenib treatment. Therefore, it is critical to elucidate the mechanisms underlying sorafenib resistance and find representative biomarkers for sorafenib treatment in RCC patients. Herein, we identified that a long noncoding RNA GAS5 was downregulated in sorafenib nonresponsive RCCs. GAS5 overexpression conferred sorafenib sensitive to nonresponsive RCC cells, whereas knockdown of GAS5 promoted responsive RCC cells resistant to sorafenib treatment in vitro and in vivo. Mechanistically, GAS5 functioned as competing endogenous RNA to repress miR-21, which controlled its down-stream target SOX5. We proposed that GAS5 was responsible for sorafenib resistance in RCC cells and GAS5 exerted its function through the miR-21/ SOX5 axis. Our findings suggested that GAS5 downregulation may be a new marker of poor response to sorafenib and GAS5 could be a potential therapeutic target for sorafenib treatment in RCC.

Effect of Neutral-pH, Low–Glucose Degradation Product Peritoneal Dialysis Solutions on Residual Renal Function, Urine Volume, and Ultrafiltration: A Systematic Review and Meta-Analysis

PubMed Central

Yohanna, Seychelle; Alkatheeri, Ali M.A.; Brimble, Scott K.; McCormick, Brendan; Iansavitchous, Arthur; Blake, Peter G.

2015-01-01

Background and objectives Neutral-pH, low–glucose degradation products solutions were developed in an attempt to lessen the adverse effects of conventional peritoneal dialysis solutions. A systematic review was performed evaluating the effect of these solutions on residual renal function, urine volume, peritoneal ultrafiltration, and peritoneal small-solute transport (dialysate to plasma creatinine ratio) over time. Design, setting, participants, & measurements Multiple electronic databases were searched from January of 1995 to January of 2013. Randomized trials reporting on any of four prespecified outcomes were selected by consensus among multiple reviewers. Results Eleven trials of 643 patients were included. Trials were generally of poor quality. The meta-analysis was performed using a random effects model. The use of neutral-pH, low-glucose degradation products solutions resulted in better preserved residual renal function at various study durations, including >1 year (combined analysis: 11 studies; 643 patients; standardized mean difference =0.17 ml/min; 95% confidence interval, 0.01 to 0.32), and greater urine volumes (eight studies; 598 patients; mean difference =128 ml/d; 95% confidence interval, 58 to 198). There was no significant difference in peritoneal ultrafiltration (seven studies; 571 patients; mean difference =−110; 95% confidence interval, −312 to 91) or dialysate to plasma creatinine ratio (six studies; 432 patients; mean difference =0.03; 95% confidence interval, 0.00 to 0.06). Conclusions The use of neutral-pH, low–glucose degradation products solutions results in better preservation of residual renal function and greater urine volumes. The effect on residual renal function occurred early and persisted beyond 12 months. Additional studies are required to evaluate the use of neutral-pH, low–glucose degradation products solutions on hard clinical outcomes. PMID:26048890

Incidence and aetiology of renal phosphate loss in patients with hypophosphatemia in the intensive care unit.

PubMed

Bech, Anneke; Blans, Michiel; Telting, Darryl; de Boer, Hans

2013-10-01

Hypophosphatemia is a common finding in patients in the intensive care unit (ICU). Its cause is often poorly understood. The aim of this study was to understand the incidence of renal phosphate loss in ICU-related hypophosphatemia, and to examine the role of phosphaturic hormones in its etiology. Plasma phosphate levels were measured on day 1, 3, 5 and 7 in 290 consecutive patients admitted to the ICU. Renal phosphate handling and phosphaturic hormones were studied in a subset of patients with phosphate levels <0.6 mmol/L. Renal phosphate loss was defined as a TmP/gfr < 0.6 mmol/L. Hypophosphatemia developed in 24% of all patients. This mainly occurred within the first 3 days of stay and in patients with serum creatinine levels <150 μmol/L. Renal phosphate loss was present in 80% of patients who developed hypophosphatemia, and was not related to serum levels of parathyroid hormone (PTH), PTH-related protein (PTH-rp), fibroblast growth factor 23 (FGF-23), or calcitonin. Hypophosphatemia in the ICU is commonly associated with renal phosphate loss. It mainly occurs within the first 3 days of admission, in particular in patients with preserved renal function. Renal phosphate loss is not explained by elevated PTH, PTH-rp, FGF-23 or calcitonin levels.

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

PubMed

Catino, Anna B; Hubbard, Rebecca A; Chirinos, Julio A; Townsend, Ray; Keefe, Stephen; Haas, Naomi B; Puzanov, Igor; Fang, James C; Agarwal, Neeraj; Hyman, David; Smith, Amanda M; Gordon, Mary; Plappert, Theodore; Englefield, Virginia; Narayan, Vivek; Ewer, Steven; ElAmm, Chantal; Lenihan, Daniel; Ky, Bonnie

2018-03-01

Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P =0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P <0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P <0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function. © 2018 American Heart Association, Inc.

Better microvascular function on long-term treatment with lisinopril than with nifedipine in renal transplant recipients.

PubMed

Asberg, A; Midtvedt, K; Vassbotn, T; Hartmann, A

2001-07-01

The prevalence of hypertension in renal transplant recipients is high but the pathophysiology is poorly defined. Impaired endothelial function may be a factor of major importance. The present study addresses the effects of long-term treatment with either lisinopril or slow-release nifedipine on microvascular function and plasma endothelin in renal transplant recipients on cyclosporin A (CsA). Seventy-five hypertensive renal transplant recipients were double-blind randomized to receive slow-release nifedipine (NIF, n=40) or lisinopril (LIS, n=35). Ten normotensive, age-matched recipients served as controls. All patients received CsA-based immunosuppressive therapy including prednisolone and azathioprine. Microvascular function was assessed in the forearm skin vasculature, using laser Doppler flowmetry in combination with post-occlusive reactive hyperaemia and endothelial-dependent function during local acetylcholine (ACh) stimulation. The analysis of microvascular function (AUC(rh)) showed that nifedipine-treated patients had significantly lower responses compared with lisinopril-treated patients (20+/-17 and 43+/-20 AU x min respectively, P=0.0016). Endothelial function was borderline significantly lower in the NIF group compared with the LIS group (640+/-345 and 817+/-404 AU x min respectively, P=0.056). The responses in the LIS group were comparable with those in non-hypertensive controls (AUC(rh) was 37+/-16 and AUC(ACh) was 994+/-566 AU x min). Plasma endothelin-1 concentrations were significantly higher in the NIF group compared with the LIS group (0.44+/-0.19 vs. 0.34+/-0.10 fmol/ml respectively, P=0.048), and were 0.29+/-0.09 fmol/ml in the control patients. AUC(ACh) was associated with plasma endothelin-1 (P=0.0053), while AUC(rh) was not (P=0.080). The study indicates that long-term treatment with lisinopril, when compared with nifedipine, yields a more beneficial effect on microvascular function in hypertensive renal transplant recipients on CsA. The beneficial microvascular effect may be mediated in part by an endothelin-1-associated effect on the endothelium.

Renal damage detected by DMSA, despite normal renal ultrasound, in children with febrile UTI.

PubMed

Bush, N C; Keays, M; Adams, C; Mizener, K; Pritzker, K; Smith, W; Traylor, J; Villanueva, C; Snodgrass, W T

2015-06-01

2011 American Academy of Pediatrics guidelines recommended renal-bladder ultrasound (RBUS) as the only evaluation after febrile urinary tract infection (FUTI) in infants aged 2-24 months. We determined the sensitivity, specificity, and false negative rate of RBUS to identify DMSA-detected renal damage in this age group as well as in older children. Consecutive patients referred to pediatric urology with a history of FUTI underwent DMSA ≥ 3 months after FUTI. Abnormal RBUS was defined as: Society of Fetal Urology hydronephrosis grades I-IV; hydroureter ≥ 7 mm; renal scar defined as focal parenchymal thinning; and/or size discrepancy ≥ 1 cm between kidneys. Abnormal DMSA was presence of any focal uptake defects and/or split renal function < 44%. We calculated sensitivity, specificity, positive and negative predictive values, and false negative rates of RBUS compared to DMSA. 618 patients (79% female), median age 3.4 years, were referred for FUTIs. Of the 512 (83%) with normal RBUS, 99 (19%) had abnormal DMSA. Children with normal RBUS after their first FUTI had abnormal DMSA in 15/151 (10%) aged ≤ 24 months and 23/119 (19%) aged > 24 months. RBUS had poor sensitivity (34%) and low positive predictive value (47%) to identify patients with renal damage. 99/149 (66%) children with renal damage on DMSA had normal RBUS. After FUTI, 66% of children with reduced renal function and/or renal cortical defects found by DMSA scintigraphy had a normal RBUS. Since abnormal DMSA may correlate with increased risk for VUR, recurrent FUTI and renal damage, our data suggest RBUS alone will fail to detect a significant proportion of patients at risk. The data suggest that imaging after FUTI should include acute RBUS and delayed DMSA, reserving VCUG for patients with abnormal DMSA and/or recurrent FUTI. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Long-term prognosis after acute kidney injury (AKI): what is the role of baseline kidney function and recovery? A systematic review.

PubMed

Sawhney, Simon; Mitchell, Mhairi; Marks, Angharad; Fluck, Nick; Black, Corrinda

2015-01-06

To summarise the evidence from studies of acute kidney injury (AKI) with regard to the effect of pre-AKI renal function and post-AKI renal function recovery on long-term mortality and renal outcomes, and to assess whether these factors should be taken into account in future prognostic studies. A systematic review of observational studies listed in Medline and EMBASE from 1990 to October 2012. All AKI studies in adults with data on baseline kidney function to identify AKI; with outcomes either stratified by pre-AKI and/or post-AKI kidney function, or described by the timing of the outcomes. Long-term mortality and worsening chronic kidney disease (CKD). Of 7385 citations, few studies met inclusion criteria, reported baseline kidney function and stratified by pre-AKI or post-AKI function. For mortality outcomes, three studies compared patients by pre-AKI renal function and six by post-AKI function. For CKD outcomes, two studies compared patients by pre-AKI function and two by post-AKI function. The presence of CKD pre-AKI (compared with AKI alone) was associated with doubling of mortality and a fourfold to fivefold increase in CKD outcomes. Non-recovery of kidney function was associated with greater mortality and CKD outcomes in some studies, but findings were inconsistent varying with study design. Two studies also reported that risk of poor outcome reduced over time post-AKI. Meta-analysis was precluded by variations in definitions for AKI, CKD and recovery. The long-term prognosis after AKI varies depending on cause and clinical setting, but it may also, in part, be explained by underlying pre-AKI and post-AKI renal function rather than the AKI episode itself. While carefully considered in clinical practice, few studies address these factors and with inconsistent study design. Future AKI studies should report pre-AKI and post-AKI function consistently as additional factors that may modify AKI prognosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Odour perception in chronic renal disease.

PubMed

Griep, M I; Van der Niepen, P; Sennesael, J J; Mets, T F; Massart, D L; Verbeelen, D L

1997-10-01

The sense of smell plays an important role in the quality of life. Many studies have shown a declining odour perception in the elderly, as well as in subjects in poor health or nutritional state. Considering the high prevalence of poor nutritional state in renal disease and the importance of odour perception in nutrition and health, the relationship between renal function, nutritional state, and odour perception is explored in this study. A total of 101 patients with chronic renal failure participated in the study. Thirty-eight haemodialysis patients (mean age = 64.3 years) were evaluated both before and after dialysis. Sixteen patients on peritoneal dialysis treatment (mean age = 64.0 years), 28 transplanted patients (mean age = 53.5 years, mean creatinine clearance = 64.0 ml/min) and 19 patients with varying degrees of renal insufficiency were also included (mean age = 63.7 years, mean creatinine clearance = 29.5 ml/min). Patients with cognitive deficits or upper respiratory airway diseases were excluded. A validated objective procedure was used to measure odour perception, by determining the detection threshold for isoamyl acetate (banana odour) as the lowest detectable odour concentration. Healthy control persons had significantly lower odour thresholds compared to patients on peritoneal (P = 0.001) and haemodialysis (P = 0.002). No significant difference was observed in odour perception between patients on peritoneal and haemodialysis (P = 0.779) and for patients on haemodialysis before and after a dialysis session. Transplanted patients had significantly better odour perception compared to matched patients on dialysis (P < 0.001). Odour perception of transplanted patients and matched healthy control persons was similar (P = 0.81). In patients with varying degrees of renal insufficiency, including healthy controls and transplanted patients, a significant positive correlation was found between odour perception and creatinine clearance (P = 0.02). A significant negative correlation was found between odour perception and serum concentration of urea (P < 0.001), serum phosphorus (P = 0.022) and protein catabolic rate (P < 0.05). Other parameters measuring nutritional status (albumin, BMI) were not correlated with odour perception. Our results show that the ability to smell is severely impaired in patients with chronic renal failure and is related to the degree of renal impairment and the degree of accumulation of uraemic toxins. After renal transplantation, patients have a normal odour perception, indicating the capacity of the olfactory system to recover once the concentration of uraemic toxins remains below a critical threshold. Acute removal of uraemic toxins by dialysis does not correct olfactory disturbances, suggesting a long lasting effect of uraemia on olfactory function.

Membranoproliferative glomerulonephritis and acute renal failure in a patient with chronic lymphocytic leukemia: Response to obinutuzumab.

PubMed

Jain, Punit; Kanagal-Shamanna, Rashmi; Wierda, William; Ferrajoli, Alessandra; Keating, Michael; Jain, Nitin

2017-09-01

Membranoproliferative glomerulonephritis (MPGN) is a common extramedullary renal presentation in chronic lymphocytic leukemia (CLL) and can present with either a frank renal failure or proteinuria. One of its etiologies has been attributed to a paraneoplastic, immune complex phenomenon occurring in CLL. Although there is no standard of care in such patients, use of anti-CD20 monoclonal antibodies like rituximab have been used before in such patients with variable responses. Obinutuzumab is a novel, type II, immunoglobulin-G1 monoclonal antibody with a higher efficacy than rituximab and has an established safely profile in patients with comorbidities and poor renal functions. There are no such reported cases of MPGN in CLL being treated with obinutuzumab. We used the standard doses of obinutuzumab in our elderly patient (78-year-old woman) with high-risk CLL due to an underlying TP53 mutation, along with a MPGN-related acute renal failure. The patient achieved complete remission after six cycles of obinutuzumab; however, she remained positive for minimal residual disease on flow cytometry. Her renal function improved completely, suggesting a complete response of her underlying MPGN. Obinutuzumab has an established safety profile in patients with CLL, but our case is the first reported case of a paraneoplastic, immune complex-mediated MPGN in CLL being treated with obinutuzumab. Obinutuzumab should be explored as a potential option in patients with CLL and MPGN. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

The utility of uric acid assay in dogs as an indicator of functional hepatic mass.

PubMed

Hill, J M; Leisewitz, A L; Goddard, A

2011-06-01

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route of excretion.

NEK8 Links the ATR-regulated Replication Stress Response and S-phase CDK Activity to Renal Ciliopathies

PubMed Central

Choi, Hyo Jei Claudia; Lin, Jia-Ren; Vannier, Jean-Baptiste; Slaats, Gisela G.; Kile, Andrew C.; Paulsen, Renee D.; Manning, Danielle K.; Beier, David R.; Giles, Rachel H.; Boulton, Simon J.; Cimprich, Karlene A.

2013-01-01

Summary Renal ciliopathies are a leading cause of kidney failure, but their exact etiology is poorly understood. NEK8/NPHP9 is a ciliary kinase associated with two renal ciliopathies in humans and mice, nephronophthisis (NPHP) and polycystic kidney disease. Here, we identify NEK8 as a key effector of the ATR-mediated replication stress response. Cells lacking NEK8 form spontaneous DNA double-strand breaks (DSBs) which further accumulate when replication forks stall, and they exhibit reduced fork rates, unscheduled origin firing, and increased replication fork collapse. NEK8 suppresses DSB formation by limiting cyclin A-associated CDK activity. Strikingly, a mutation in NEK8 that is associated with renal ciliopathies affects its genome maintenance functions. Moreover, kidneys of NEK8 mutant mice accumulate DNA damage, and loss of NEK8 or replication stress similarly disrupts renal cell architecture in a 3D-culture system. Thus, NEK8 is a critical component of the DNA damage response that links replication stress with cystic kidney disorders. PMID:23973373

Mitochondrial-targeted antioxidants represent a promising approach for prevention of cisplatin-induced nephropathy

PubMed Central

Mukhopadhyay, Partha; Horváth, Béla; Zsengellér, Zsuzsanna; Zielonka, Jacek; Tanchian, Galin; Holovac, Eileen; Kechrid, Malek; Patel, Vivek; Stillman, Isaac E.; Parikh, Samir M.; Joseph, Joy; Kalyanaraman, Balaraman; Pacher, Pál

2011-01-01

Cisplatin is a widely used anti-neoplastic agent; however, its major limitation is the development of dose-dependent nephrotoxicity whose precise mechanisms are poorly understood. Here we show that mitochondrial dysfunction is not only a feature of cisplatin nephrotoxicity, but that targeted delivery of superoxide dismutase mimetics to mitochondria largely prevents the renal effects of cisplatin. Cisplatin induced renal oxidative stress, deterioration of mitochondrial structure and function, an intense inflammatory response, histopathological injury, and renal dysfunction. A single systemic dose of mitochondrially-targeted antioxidants, MitoQ or Mito-CP, dose-dependently prevented cisplatin-induced renal dysfunction. Mito-CP also prevented mitochondrial injury and dysfunction, renal inflammation, and tubular injury and apoptosis. Despite being broadly renoprotective against cisplatin, Mito-CP did not diminish cisplatin’s anti-neoplastic effect in a human bladder cancer cell line. Our results highlight the central role of mitochondrially generated oxidants in the pathogenesis of cisplatin nephrotoxicity. Since similar compounds appear to be safe in humans, mitochondrially-targeted antioxidants may represent a novel therapeutic approach against cisplatin nephrotoxicity. PMID:22120494

Cerebro-renal interactions: impact of uremic toxins on cognitive function.

PubMed

Watanabe, Kimio; Watanabe, Tsuyoshi; Nakayama, Masaaki

2014-09-01

Cognitive impairment (CI) associated with chronic kidney disease (CKD) has received attention as an important problem in recent years. Causes of CI with CKD are multifactorial, and include cerebrovascular disease, renal anemia, secondary hyperparathyroidism, dialysis disequilibrium, and uremic toxins (UTs). Among these causes, little is known about the role of UTs. We therefore selected 21 uremic compounds, and summarized reports of cerebro-renal interactions associated with UTs. Among the compounds, uric acid, indoxyl sulfate, p-cresyl sulfate, interleukin 1-β, interleukin 6, TNF-α, and PTH were most likely to affect the cerebro-renal interaction dysfunction; however, sufficient data have not been obtained for other UTs. Notably, most of the data were not obtained under uremic conditions; therefore, the impact and mechanism of each UT on cognition and central nervous system in uremic state remains unknown. At present, impacts and mechanisms of UT effects on cognition are poorly understood. Clarifying the mechanisms and establishing novel therapeutic strategies for cerebro-renal interaction dysfunction is expected to be subject of future research. Copyright © 2014 Elsevier Inc. All rights reserved.

Anemia and Long-Term Renal Prognosis in Patients with Post-Renal Acute Kidney Injury of Nonmalignant Cause.

PubMed

Sasaki, Sho; Kawarazaki, Hiroo; Hasegawa, Takeshi; Shima, Hideaki; Naganuma, Toshihide; Shibagaki, Yugo

2017-01-01

The renal prognosis of post-renal acute kidney injury (PoR-AKI) has not been verified so far. The objective of this study was to assess the association of baseline anemia with long-term renal prognosis in patients with PoR-AKI. We performed a multicenter retrospective cohort study. Consecutive adult patients from December 2006 to February 2010, who met the requirements as mentioned in the definition of PoR-AKI, were included. Patients without data on baseline renal function and at 6 months after PoR-AKI were excluded. We set baseline hemoglobin (Hb) level (g/dl) as the main exposure to be tested. The main outcome measure was long-term renal prognosis as determined by the difference between proximate estimated glomerular filtration rate (eGFR) at 6 months after diagnosis of PoR-AKI and baseline eGFR prior to the occurrence of the present PoR-AKI (ΔeGFR after 6 months) using the general linear model. We included 136 patients with PoR-AKI. The most frequent cause of PoR-AKI was malignancy, accounting for 39.0% (n = 53) of cases. Multivariate analysis adjusted for possible confounders showed that ΔeGFR after 6 months significantly changed by -4.28 ml/min/1.73 m2 for every 1 g/dl lower Hb at diagnosis (95% CI 1.86-6.69, p < 0.01). An additional multivariate analysis that was stratified by the presence or absence of malignancy as the cause of PoR-AKI yielded the same significant result only in the stratum of the nonmalignant cause of PoR-AKI. Patients with a nonmalignant cause of PoR-AKI who have baseline anemia may have poor long-term renal prognosis. In these cases, close observation of renal function after renal recovery may be required. © 2016 S. Karger AG, Basel.

Renal dysfunction in liver cirrhosis and its correlation with Child-Pugh score and MELD score

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Gurning, M.

2018-03-01

Renal dysfunction (RD) is a serious and common complication in a patient with liver cirrhosis. It provides a poor prognosis. The aim of our study was to evaluate the renal function in liver cirrhosis, also to determine the correlation with the graduation of liver disease assessed by Child-Pugh Score (CPS) and MELD score. This was a cross-sectional study included patients with liver cirrhosis admitted to Adam Malik Hospital Medan in June - August 2016. We divided them into two groups as not having renal dysfunction (serum creatinine < 1.5 mg/dL) and having renal dysfunction (serum creatinine ≤ 1.5 mg/dL). For the processing of data, SPSS 22.0 was used. Statistical methods used: Chi-square, Fisher exact, one way ANOVA, Kruskal Wallis test and Pearson coefficient of correlation. The level of significance was p<0.05. 55 patients with presented with renal dysfunction were 16 (29.1 %). There was statistically significant inverse correlation between GFR and CPS (r = -0.308), GFR and MELD score (r = -0.278). There was a statistically significant correlation between creatinine and MELD score (r = 0.359), creatinine and CPS (r = 0.382). The increase of the degree of liver damage is related to the increase of renal dysfunction.

Structural Predictors of Loss of Renal Function in American Indians with Type 2 Diabetes.

PubMed

Fufaa, Gudeta D; Weil, E Jennifer; Lemley, Kevin V; Knowler, William C; Brosius, Frank C; Yee, Berne; Mauer, Michael; Nelson, Robert G

2016-02-05

Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued. Renal function loss was defined as ≥40% loss of GFR from the research examination performed at the time of kidney biopsy. Associations with renal function loss were evaluated by Cox proportional hazards regression. Hazard ratios (HRs) were reported per 1-SD increment for each morphometric variable. Of 111 participants (82% women; baseline mean [±SD] age, 46 years old [±10]; diabetes duration, 16 years [±6]; hemoglobin A1c =9.4% [±2.2]; GFR=147 ml/min [±56]; median albumin-to-creatinine ratio, 41 mg/g [interquartile range, 13-158]), 51 (46%) developed renal function loss during a median follow-up of 6.6 years (interquartile range, 3.1-9.0). Fourteen had baseline GFR <90 ml/min, and three had baseline GFR <60 ml/min. Higher mesangial fractional volume (HR, 2.27; 95% confidence interval [95% CI], 1.58 to 3.26), percentage of global glomerular sclerosis (HR, 1.63; 95% CI, 1.21 to 2.21), nonpodocyte cell number per glomerulus (HR, 1.50; 95% CI, 1.10 to 2.05), glomerular basement membrane width (HR, 1.48; 95% CI, 1.05 to 2.08), mean glomerular volume (HR, 1.42; 95% CI, 1.02 to 1.96), and podocyte foot process width (HR, 1.28; 95% CI, 1.03 to 1.60); lower glomerular filtration surface density (HR, 0.62; 95% CI, 0.41 to 0.94); and fewer endothelial fenestrations (HR, 0.68; 95% CI, 0.48 to 0.95) were each associated with GFR decline after adjustment for baseline age, sex, duration of diabetes, hemoglobin A1c, GFR, and treatment assignment during the clinical trial. Quantitative measures of glomerular structure predict loss of renal function in type 2 diabetes. Copyright © 2016 by the American Society of Nephrology.

Impact of worsening renal function related to medication in heart failure.

PubMed

Brunner-La Rocca, Hans-Peter; Knackstedt, Christian; Eurlings, Luc; Rolny, Vinzent; Krause, Friedemann; Pfisterer, Matthias E; Tobler, Daniel; Rickenbacher, Peter; Maeder, Micha T

2015-02-01

Renal failure is a major challenge in treating heart failure (HF) patients. HF medication may deteriorate renal function, but the impact thereof on outcome is unknown. We investigated the effects of HF medication on worsening renal function (WRF) and the relationship to outcome. This post-hoc analysis of TIME-CHF (NT-proBNP-guided vs. symptom-guided management in chronic HF) included patients with LVEF ≤45% and ≥1 follow-up visit (n = 462). WRF III was defined as a rise in serum creatinine ≥0.5 mg/dL (i.e. 44.2 µmol/L) at any time during the first 6 months. Four classes of medication were considered: loop diuretics, beta-blockers, renin-angiotensin system (RAS)-blockers, and spironolactone. Functional principal component analysis of daily doses was used to comprehend medication over time. All-cause mortality after 18 months was the primary outcome. Interactions between WRF, medication, and outcome were tested. Patients with WRF III received on average higher loop diuretic doses (P = 0.0002) and more spironolactone (P = 0.02), whereas beta-blockers (P = 0.69) did not differ and lower doses of RAS-blockers were given (P = 0.09). There were significant interactions between WRF III, medicationn and outcome. Thus, WRF III was associated with poor prognosis if high loop diuretic doses were given (P = 0.001), but not with low doses (P = 0.29). The opposite was found for spironolactone (poor prognosis in the case of WRF III with no spironolactone, P <0.0001; but not with spironolactone, P = 0.31). Beta-blockers were protective in all patients (P <0.001), but most in those with WRF III (P <0.05 for interaction). RAS-blockade was associated with improved outcome (P = 0.006), irrespective of WRF III. Based on this analysis, it may be hypothesized that high doses of loop diuretics might have detrimental effects, particularly in combination with significant WRF, whereas spironolactone and beta-blockers might be protective in patients with WRF. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland.

PubMed

Brocklebank, Vicky; Johnson, Sally; Sheerin, Thomas P; Marks, Stephen D; Gilbert, Rodney D; Tyerman, Kay; Kinoshita, Meredith; Awan, Atif; Kaur, Amrit; Webb, Nicholas; Hegde, Shivaram; Finlay, Eric; Fitzpatrick, Maggie; Walsh, Patrick R; Wong, Edwin K S; Booth, Caroline; Kerecuk, Larissa; Salama, Alan D; Almond, Mike; Inward, Carol; Goodship, Timothy H; Sheerin, Neil S; Marchbank, Kevin J; Kavanagh, David

2017-11-01

Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange-treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody-targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody-mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Lifestyle intervention to improve quality of life and prevent weight gain after renal transplantation: Design of the Active Care after Transplantation (ACT) randomized controlled trial.

PubMed

Klaassen, Gerald; Zelle, Dorien M; Navis, Gerjan J; Dijkema, Desie; Bemelman, Frederike J; Bakker, Stephan J L; Corpeleijn, Eva

2017-09-15

Low physical activity and reduced physical functioning are common after renal transplantation, resulting in a reduced quality of life. Another common post-transplantation complication is poor cardio-metabolic health, which plays a main role in long-term outcomes in renal transplant recipients (RTR). It is increasingly recognized that weight gain in the first year after transplantation, especially an increase in fat mass, is a highly common contributor to cardio-metabolic risk. The aim of this study is to compare the outcomes of usual care to the effects of exercise alone, and exercise combined with dietary counseling, on physical functioning, quality of life and post-transplantation weight gain in RTR. The Active Care after Transplantation study is a multicenter randomized controlled trial with three arms in which RTR from 3 Dutch hospitals are randomized within the first year after transplantation to usual care, to exercise intervention (3 months supervised exercise 2 times per week followed by 12 months active follow-up), or to an exercise + diet intervention, consisting of the exercise training with additional dietary counseling (12 sessions over 15 months by a renal dietician). In total, 219 participants (73 per group) will be recruited. The primary outcome is the subdomain physical functioning of quality of life, (SF-36 PF). Secondary outcomes include other evaluations of quality of life (SF-36, KDQOL-SF, EQ-5D), objective measures of physical functioning (aerobic capacity and muscle strength), level of physical activity, gain in adiposity (body fat percentage by bio-electrical impedance assessment, BMI, waist circumference), and cardiometabolic risk factors (blood pressure, lipids, glucose metabolism). Furthermore, data on renal function, medical history, medication, psychological factors (motivation, kinesiophobia, coping style), nutrition knowledge, nutrition intake, nutrition status, fatigue, work participation, process evaluation and cost-effectiveness are collected. Evidence on the effectiveness of an exercise intervention, or an exercise + diet intervention on physical functioning, weight gain and cardiometabolic health in RTR is currently lacking. The outcomes of the present study may help to guide future evidence-based lifestyle care after renal transplantation. Number: NCT01047410 .

Contrast medium administration and image acquisition parameters in renal CT angiography: what radiologists need to know.

PubMed

Saade, Charbel; Deeb, Ibrahim Alsheikh; Mohamad, Maha; Al-Mohiy, Hussain; El-Merhi, Fadi

2016-01-01

Over the last decade, exponential advances in computed tomography (CT) technology have resulted in improved spatial and temporal resolution. Faster image acquisition enabled renal CT angiography to become a viable and effective noninvasive alternative in diagnosing renal vascular pathologies. However, with these advances, new challenges in contrast media administration have emerged. Poor synchronization between scanner and contrast media administration have reduced the consistency in image quality with poor spatial and contrast resolution. Comprehensive understanding of contrast media dynamics is essential in the design and implementation of contrast administration and image acquisition protocols. This review includes an overview of the parameters affecting renal artery opacification and current protocol strategies to achieve optimal image quality during renal CT angiography with iodinated contrast media, with current safety issues highlighted.

Transarterial chemoembolization in patients with hepatocellular carcinoma and renal insufficiency.

PubMed

Hsu, Chia-Yang; Huang, Yi-Hsiang; Su, Chien-Wei; Chiang, Jen-Huey; Lin, Han-Chieh; Lee, Pui-Ching; Lee, Fa-Yauh; Huo, Teh-Ia; Lee, Shou-Dong

2010-09-01

Renal dysfunction is often present in patients with cirrhosis and hepatocellular carcinoma (HCC). Acute renal failure (ARF) may occur after transarterial chemoembolization (TACE) owing to radiocontrast agent. This study investigated the incidence and risk factors of ARF and prognostic predictors in HCC patients with preexisting renal insufficiency undergoing TACE. A total of 566 HCC patients undergoing TACE were enrolled. Renal insufficiency was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m. In a mean follow-up duration of 18+/-16 months, 231 (40.8%) patients undergoing TACE died. Renal insufficiency that was present in 134 (23.7%) patients at baseline, independently predicted a poor prognosis in the Cox proportional hazards model [risk ratio (RR): 1.47, P=0.012]. Of them, 13 (10%) and 6 (5%) patients had transient and prolonged ARF after TACE, respectively. Post-TACE gastrointestinal bleeding [odds ratio (OR): 16.54, P=0.001] and higher Cancer of the Liver Italian Program (CLIP) scores (> or =2; OR: 4.22, P=0.02) were independent risk factors for ARF in the multivariate logistic regression analysis. In the Cox model, prolonged ARF (RR: 3.28, P<0.001) and higher CLIP scores (> or =2; RR: 2.13, P<0.001) were independent poor prognostic predictors for HCC patients with renal insufficiency receiving TACE. Gastrointestinal bleeding and higher CLIP scores are associated with the development of ARF in patients with HCC and renal insufficiency undergoing TACE. Higher CLIP scores and renal insufficiency, either preexisting before TACE or as a complication of TACE, are poor prognostic predictors in HCC patients receiving TACE.

[Renal arterial spin labeling magnetic resonance imaging in normal adults: a study with a 3.0 T scanner].

PubMed

Zhang, Fan; Zhang, Xuelin; Yang, Li; Shen, Jie; Gao, Wei

2013-10-01

To analyze the renal relative blood flow value (rBFV) and image quality in normal adults using single-shot fast spin echo, flow sensitive invention recovery (SSFSE-FAIR) magnetic resonance (MR) sequence and echo planar imaging, and flow sensitive invention recovery (EPI-FAIR) MR sequence, and assess its value for clinical application in routine renal examination. Forty volunteers (25 male and 15 female adults, aged 30 to 62 years) with normal renal function were included in this prospective study. All the subjects underwent 3.0 Tesla MR scanning using 3 MR scan modes, namely breath-holding EPI-FAIR, breath-holding SSFSE-FAIR and free breathing SSFSE-FAIR. SSFSE-FAIR without breath-holding was capable of differentiating the renal cortex and medulla with the corresponding rBFVs of 111.48∓9.23 and 94.98∓3.38, respectively. Breath-holding SSFSE-FAIR and EPI-FAIR failed to distinguish the borders of the renal cortex and medulla. The EPI-FAIR rBFV of mixed cortex and medulla value was 178.50∓17.17 (95%CI: 167.59, 189.41). Breath-holding SSFSE-FAIR and EPI-FAIR can not distinguish the renal cortex and medulla due to a poor spatial resolution but can be used for rough evaluation of renal blood perfusion. Free breathing SSFSE-FAIR with an improved spatial resolution allows evaluation of the status of renal perfusion of the cortex and medulla.

Correlation between differential renal function estimation using CT-based functional renal parenchymal volume and (99m)Tc - DTPA renal scan.

PubMed

Sarma, Debanga; Barua, Sasanka K; Rajeev, T P; Baruah, Saumar J

2012-10-01

Nuclear renal scan is currently the gold standard imaging study to determine differential renal function. We propose helical CT as single modality for both the anatomical and functional evaluation of kidney with impaired function. In the present study renal parenchymal volume is measured and percent total renal volume is used as a surrogate marker for differential renal function. The objective of this study is to correlate between differential renal function estimation using CT-based renal parenchymal volume measurement with differential renal function estimation using (99m)TC - DTPA renal scan. Twenty-one patients with unilateral obstructive uropathy were enrolled in this prospective comparative study. They were subjected to (99m)Tc - DTPA renal scan and 64 slice helical CT scan which estimates the renal volume depending on the reconstruction of arterial phase images followed by volume rendering and percent renal volume was calculated. Percent renal volume was correlated with percent renal function, as determined by nuclear renal scan using Pearson coefficient. RESULTS AND OBSERVATION: A strong correlation is observed between percent renal volume and percent renal function in obstructed units (r = 0.828, P < 0.001) as well as in nonobstructed units (r = 0.827, P < 0.001). There is a strong correlation between percent renal volume determined by CT scan and percent renal function determined by (99m)TC - DTPA renal scan both in obstructed and in normal units. CT-based percent renal volume can be used as a single radiological tests for both functional and anatomical assessment of impaired renal units.

Congenital ureteropelvic junction obstruction: physiopathology, decoupling of tout court pelvic dilatation-obstruction semantic connection, biomarkers to predict renal damage evolution.

PubMed

Alberti, C

2012-02-01

The widespread use of fetal ultrasonography results in a frequent antenatally observation of hydronephrosis, ureteropelvic junction obstruction (UPJO) accounting for the greatest fraction of congenital obstructive nephropathy. UPJO may be considered, in most cases, as a functional obstructive condition, depending on defective fetal smooth muscle/nerve development at this level, with lack of peristaltic wave propagation--aperistaltic segment--and, therefore, poor urine ejection from the renal pelvis into the ureter. The UPJO-related physiopathologic events are, at first, the compliant dilatation of renal pelvis that, acting as hydraulic buffer, protects the renal parenchyma from the rising intrapelvic pressure-related potential damages, and, subsequently, beyond such phase of dynamic balance, the tubular cell stretch-stress induced by increased intratubular pressure and following parenchymal inflammatory lesions: inflammatory infiltrates, fibroblast proliferation, activation of myofibroblasts, tubulo-interstitial fibrosis. Reactive oxygen species (ROS), nitric oxide (NO), several chemo- and cytokines, growth factors, prostaglandins and eicosanoids, angiotensin-II are the main pathogenetic mediators of the obstructive nephropathy. Apoptosis of tubular cells is the major cause of the tubular atrophy, together with epithelial-mesenchymal transdifferentiation. Some criticisms on tout court semantic renal pelvis dilatation-obstruction connection have been raised considering that the renal pelvis expansion isn't, in any case, linked to an ostructive condition, as it may be verified by diuretic (furosemide) renogram together with scintiscan-based evaluation of differential renal function. In this regard, rather than repetitive invasive nuclear procedures that expose the children to ionizing radiations, an intriguing noninvasive strategy, based on the evaluation of urinary biomarkers and urinary proteome, can define the UPJO-related possible progress of parenchymal lesions, thus predicting which patients must require an obstruction correcting surgery and in which patients, instead, the hydronephrosis will spontaneously resolve.

Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers.

PubMed

Pruijm, Menno; Hofmann, Lucie; Charollais-Thoenig, Julie; Forni, Valentina; Maillard, Marc; Coristine, Andrew; Stuber, Matthias; Burnier, Michel; Vogt, Bruno

2013-09-01

Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

Transcatheter Arterial Embolization with a Mixture of Absolute Ethanol and Iodized Oil for Poorly Visualized Endophytic Renal Masses Prior to CT-Guided Percutaneous Cryoablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michimoto, Kenkichi, E-mail: michikoo@jikei.ac.jp; Shimizu, Kanichiro; Kameoka, Yoshihiko

PurposeTo retrospectively evaluate the feasibility of transcatheter arterial embolization (TAE) using a mixture of absolute ethanol and iodized oil to improve localization of endophytic renal masses on unenhanced computed tomography (CT) prior to CT-guided percutaneous cryoablation (PCA).Materials and MethodsOur institutional review board approved this retrospective study. From September 2011 to June 2015, 17 patients (mean age, 66.8 years) with stage T1a endophytic renal masses (mean diameter, 26.5 mm) underwent TAE using a mixture of absolute ethanol and iodized oil to improve visualization of small and endophytic renal masses on unenhanced CT prior to CT-guided PCA. TAE was considered successful that accumulated iodizedmore » oil depicted whole of the tumor edge on CT. PCA was considered successful when the iceball covered the entire tumor with over a 5 mm margin. Oncological and renal functional outcomes and complications were also evaluated.ResultsTAE was successfully performed in 16 of 17 endophytic tumors. The 16 tumors were performed under CT-guided PCA with their distinct visualization of localization and safe ablated margin. During the mean follow-up period of 15.4 ± 5.1 months, one patient developed local recurrence. Estimated glomerular filtration rate declined by 8 % with statistical significance (P = 0.01). There was no procedure-related significant complication.ConclusionTAE using a mixture of absolute ethanol and iodized oil to improve visualization of endophytic renal masses facilitated tumor localization on unenhanced CT, permitting depiction of the tumor edge as well as a safe margin for ablation during CT-guided PCA, with an acceptable decline in renal function.« less

Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury

PubMed Central

Vilay, A Mary; Churchwell, Mariann D; Mueller, Bruce A

2008-01-01

Decreased renal drug clearance is an obvious consequence of acute kidney injury (AKI). However, there is growing evidence to suggest that nonrenal drug clearance is also affected. Data derived from human and animal studies suggest that hepatic drug metabolism and transporter function are components of nonrenal clearance affected by AKI. Acute kidney injury may also impair the clearance of formed metabolites. The fact that AKI does not solely influence kidney function may have important implications for drug dosing, not only of renally eliminated drugs but also of those that are hepatically cleared. A review of the literature addressing the topic of drug metabolism and clearance alterations in AKI reveals that changes in nonrenal clearance are highly complicated and poorly studied, but they may be quite common. At present, our understanding of how AKI affects drug metabolism and nonrenal clearance is limited. However, based on the available evidence, clinicians should be cognizant that even hepatically eliminated drugs and formed drug metabolites may accumulate during AKI, and renal replacement therapy may affect nonrenal clearance as well as drug metabolite clearance. PMID:19040780

Nephrolithiasis and hematuria--sometimes a stony road to diagnosis.

PubMed

Sellin, L; Quack, I; Weiner, S M; Waldherr, R; Henning, B; Hofebauer, S; Rump, L C

2005-08-01

We report a case of a young man with a history of kidney stones. Occurrence of gross hematuria several months after the extracorporeal shock wave, lithotripsy (ESWL) treatment lead to hospitalization. By ultrasound and abdominal CT scan, the urologist could exclude post-renal causes of the gross hematuria and acute renal failure. After transfer to a department of nephrology hemodialysis was started, an immediate kidney biopsy was performed and prednisolone was administered on the same day. The kidney biopsy revealed an anti-glomerular basement membrane (GBM) disease. The renal function did not recover and the patient remained on hemodialysis. In the literature it has been hypothesized that ESWL-treated patients are prone to develop anti-GBM disease by liberation of glomerular basement antigen through the ESWL high energy shock waves. An additional hypothesis considering the higher susceptibility for anti-GBM disease among certain HLA-tissue types is discussed with regard to our case. Unfortunately, the prolonged track to diagnosis and delayed immunosuppressive treatment could not prevent poor clinical outcome. Although anti-GBM disease is a rather rare disease, it should be included as a differential diagnosis for hematuria--especially months after ESWL treatment. Otherwise early diagnosis may be missed and as in our patient immunosuppressive treatment will remain unsuccessful to recover renal function.

The Smad3/Smad4/CDK9 complex promotes renal fibrosis in mice with unilateral ureteral obstruction.

PubMed

Qu, Xinli; Jiang, Mengjie; Sun, Yu Bo Yang; Jiang, Xiaoyun; Fu, Ping; Ren, Yi; Wang, Die; Dai, Lie; Caruana, Georgina; Bertram, John F; Nikolic-Paterson, David J; Li, Jinhua

2015-12-01

Transforming growth factor-β1 (TGF-β1)/Smad signaling has a central role in the pathogenesis of renal fibrosis. Smad3 and Smad4 are pro-fibrotic, while Smad2 is anti-fibrotic. However, these Smads form heterogeneous complexes, the functions of which are poorly understood. Here we studied Smad complex function in renal fibrosis using the mouse model of unilateral ureteric obstruction. Mice heterozygous for Smad3/4 (Smad3/4 +/- ) exhibited substantial protection from renal fibrosis through day 7 of obstruction, whereas Smad2/3 +/- and Smad2/4 +/- mice showed only modest protection. Formation of Smad3/Smad4/CDK9 complexes was an early event following obstruction in wild-type mice, which involved nuclear phosphorylation of the linker regions of Smad3. Significantly, Smad3 or Smad4 deficiency decreased the formation of Smad4/CDK9 or Smad3/CDK9 complex, Smad3 linker phosphorylation, and fibrosis but at different degrees. In vitro, TGF-β1 stimulation of collagen I promoter activity involved formation of Smad3/Smad4/CDK9 complexes, and overexpression of each component gave additive increases in collagen promoter activity. Co-administration of a CDK9 inhibitor and Smad3-specific inhibition achieved better protection from TGF-β1-induced fibrotic response in vitro and renal interstitial fibrosis in vivo. Thus formation of Smad3/Smad4/CDK9 complex drives renal fibrosis during ureteral obstruction. Formation of this complex represents a novel target for antifibrotic therapies.

Contrast medium administration and image acquisition parameters in renal CT angiography: what radiologists need to know

PubMed Central

Saade, Charbel; Deeb, Ibrahim Alsheikh; Mohamad, Maha; Al-Mohiy, Hussain; El-Merhi, Fadi

2016-01-01

Over the last decade, exponential advances in computed tomography (CT) technology have resulted in improved spatial and temporal resolution. Faster image acquisition enabled renal CT angiography to become a viable and effective noninvasive alternative in diagnosing renal vascular pathologies. However, with these advances, new challenges in contrast media administration have emerged. Poor synchronization between scanner and contrast media administration have reduced the consistency in image quality with poor spatial and contrast resolution. Comprehensive understanding of contrast media dynamics is essential in the design and implementation of contrast administration and image acquisition protocols. This review includes an overview of the parameters affecting renal artery opacification and current protocol strategies to achieve optimal image quality during renal CT angiography with iodinated contrast media, with current safety issues highlighted. PMID:26728701

Functions of the Renal Nerves.

ERIC Educational Resources Information Center

Koepke, John P.; DiBona, Gerald F.

1985-01-01

Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…

Association of haemodynamic changes measured by serial central venous saturation during ultrafiltration for acutely decompensated heart failure with diuretic resistance and change in renal function.

PubMed

Vazir, Ali; Simpkin, Victoria L; Marino, Philip; Ludman, Andrew; Banya, Winston; Tavazzi, Guido; Bastin, Anthony J; Trenfield, Sarah; Ghori, Arshad; Alexander, Peter D; Griffiths, Mark; Price, Susanna; Sharma, Rakesh; Cowie, Martin R

2016-10-01

Patients with acute decompensated heart failure with diuretic resistance (ADHF-DR) have a poor prognosis. The aim of this study was to assess in patients with ADHF-DR, whether haemodynamic changes during ultrafiltration (UF) are associated with changes in renal function (Δcreatinine) and whether Δcreatinine post UF is associated with mortality. Seventeen patients with ADHF-DR underwent 20 treatments with UF. Serial bloods (4-6 hourly) from the onset of UF treatment were measured for renal function, electrolytes and central venous saturation (CVO2). Univariate and multivariate analysis were performed to assess the relationship between changes in markers of haemodynamics [heart rate (HR), systolic blood pressure (SBP), packed cell volume (PCV) and CVO2] and Δcreatinine. Patients were followed up and mortality recorded. Cox-regression survival analysis was performed to determine covariates associated with mortality. Renal function worsened after UF in 17 of the 20 UF treatments (baseline vs. post UF creatinine: 164±58 vs. 185±69μmol/l, P<0.01). ΔCVO2 was significantly associated with Δcreatinine [β-coefficient of -1.3 95%CI (-1.8 to -0.7), P<0.001] and remained significantly associated with Δcreatinine after considering changes in SBP, HR and PCV [P<0.001]. Ten (59%) patients died at 1-year and 15(88%) by 2-years. Δcreatinine was independently associated with mortality (adjusted-hazard ratio 1.03 (1.01 to 1.07) per 1μmol/l increase in creatinine; P=0.02). Haemodynamic changes during UF as measured by the surrogate of cardiac output was associated with Δcreatinine. Worsening renal function at end of UF treatment occurred in the majority of patients and was associated with mortality. Copyright © 2016. Published by Elsevier Ireland Ltd.

Improvement in renal functions with transcatheter aortic valve implantation

PubMed Central

Keleş, Telat; Ayhan, Hüseyin; Durmaz, Tahir; Sarı, Cenk; Aslan, Abdullah Nabi; Erdoğan, Kemal Eşref; Kasapkara, Hacı Ahmet; Bilen, Emine; Bayram, Nihal Akar; Akçay, Murat; Bozkurt, Engin

2013-01-01

Background & Objectives In recent years, emerging transcatheter aortic valve implantation (TAVI) has become an alternative for surgery. However, with advanced age, several co-morbid factors together with contrast agent usage can cause deterioration in renal function and increase in the risk of acute kidney injury (AKI) with poor prognosis in patients with AKI. Therefore, many patients cannot benefit from this treatment. In this study, we aim to examine the effects of TAVI on renal functions. Methods and Results Seventy patients, mean age of 77.6 years, underwent TAVI between July 2011 and December 2012. Estimated glomerular filtration rate (eGFR) was calculated by using the Cockcroft and Gault Formula. Patients were monitored for 48 h for urine output. Stage 1 AKI, according to the VARC-2 AKIN system, developed in only five (7.1%) of the patients after the procedure. There was a statistically significant increase between the mean 1st month eGFRs before (68.2 vs. 61.0, P < 0.01) and after (68.2 vs. 63.6, P < 0.05) the TAVI in the cohort. After TAVI (48.5 mL/min, P < 0.01) and the 1st month (52.1 mL/min, P < 0.01), the eGFR of the 36 (51.4%) patients diagnosed with chronic kidney disease before the procedure showed a statistically significant increase in renal functions. The hospital mortality rate was higher in the group which developed AKI (P < 0.01). First month eGFR showed a more statistically significant increase than pre-TAVI eGFR (62.8 and 69.8, P < 0.05, respectively) in AKI developing patients and this difference - though statistically not significant - continued into the sixth month. Conclusions In this study, we showed that the treatment of aortic stenosis through TAVI allows improvement of renal functions, and that AKI rates will be lower with careful patient selection, proper pre-procedural hydration, and careful use of contrast agent. PMID:24454323

[Outcome of rapidly progressive glomerulonephritis post-streptococcal disease in children].

PubMed

Jellouli, Manel; Maghraoui, Sondos; Abidi, Kamel; Hammi, Yosra; Goucha, Rim; Naija, Ouns; Zarrouk, Chokri; Gargah, Tahar

2015-11-01

Rapidly progressive glomerulonephritis is a rare form of postinfectious glomerulonephritis. The aim of this study was to describe the outcome of our patients with severe post-streptococcal glomerulonephritis. This retrospective study was conducted in the department of pediatrics in Charles-Nicolle Hospital during a period of 13 years (1997-2009). Twenty-seven children were identified. The mean age was 8.7 years. All patients presented renal failure at presentation. The mean serum creatinine at presentation was 376.9 μmol/L. Six patients presented nephrotic syndrome. Twenty-six children had renal biopsies. Renal biopsies showed crescents in 24 cases. Eighteen children received pulse dose of corticosteroids (66.6%) and 6 children (22%) received pulse dose of corticosteroids and cyclophosphamide. Eleven patients required dialysis. At last follow-up, 22 patients (81.5%) had normal kidney function, 2 had renal dysfunction and 3 reached end stage renal disease. The only significant determinant for renal survival was the supportive dialysis (P=0.015). Rapidly progressive glomerulonephritis is uncommon. There have been significant advancements in supportive, as well as specific therapy, but the outcome continues to be poor. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Direct peritoneal resuscitation improves obesity-induced hepatic dysfunction after trauma.

PubMed

Matheson, Paul J; Franklin, Glen A; Hurt, Ryan T; Downard, Cynthia D; Smith, Jason W; Garrison, Richard N

2012-04-01

The metabolic syndrome and associated fatty liver disease are thought to contribute to poor outcomes in trauma patients. Experimentally, obesity compromises liver blood flow. We sought to correlate the effect of obesity, injury severity, and liver dysfunction with trauma outcomes. We hypothesized that obesity-related liver dysfunction could be mitigated with the novel technique of adjunctive direct peritoneal resuscitation (DPR). This study has clinical and experimental arms. The clinical study was a case-controlled retrospective analysis of ICU trauma patients (n = 72 obese, n = 187 nonobese). The experimental study was a hemorrhagic shock model in obese rats to assess the effect of DPR on liver blood flow, liver function, and inflammatory mediators. In trauma patients, univariate and multivariate analyses demonstrated increasing mortality (p < 0.05), septic complications (p < 0.05), liver dysfunction (p < 0.001), and renal impairment (p < 0.05) with increasing body mass index and injury severity score. Obesity in rats impairs liver blood flow, liver function, renal function, and inflammation (interleukin [IL]-1β, IL-6, high mobility group protein B1[HMGB-1]). The addition of DPR to shock resuscitation restores liver blood flow, improves organ function, and reverses the systemic proinflammatory response. Our clinical review substantiates that obesity worsens trauma outcomes regardless of injury severity. Obesity-related liver and renal dysfunction is aggravated by injury severity. In an obese rat model of resuscitated hemorrhagic shock, the addition of DPR abrogates trauma-induced liver, renal, and inflammatory responses. We conclude that the addition of DPR to the clinical resuscitation regimen will benefit the obese trauma patient. Published by Elsevier Inc.

A scheme based on ICD-10 diagnoses and drug prescriptions to stage chronic kidney disease severity in healthcare administrative records.

PubMed

Friberg, Leif; Gasparini, Alessandro; Carrero, Juan Jesus

2018-04-01

Information about renal function is important for drug safety studies using administrative health databases. However, serum creatinine values are seldom available in these registries. Our aim was to develop and test a simple scheme for stratification of renal function without access to laboratory test results. Our scheme uses registry data about diagnoses, contacts, dialysis and drug use. We validated the scheme in the Stockholm CREAtinine Measurements (SCREAM) project using information on approximately 1.1 million individuals residing in the Stockholm County who underwent calibrated creatinine testing during 2006-11, linked with data about health care contacts and filled drug prescriptions. Estimated glomerular filtration rate (eGFR) was calculated with the CKD-EPI formula and used as the gold standard for validation of the scheme. When the scheme classified patients as having eGFR <30 mL/min/1.73 m 2 , it was correct in 93.5% of cases. The specificity of the scheme was close to 100% in all age groups. The sensitivity was poor, ranging from 68.2% in the youngest age quartile, down to 10.7% in the oldest age quartile. Age-related decline in renal function makes a large proportion of elderly patients fall into the chronic kidney disease (CKD) range without receiving CKD diagnoses, as this often is seen as part of normal ageing. In the absence of renal function tests, our scheme may be of value for identifying patients with moderate and severe CKD on the basis of diagnostic and prescription data for use in studies of large healthcare databases.

Long term outcome of treatment of end stage renal failure.

PubMed

Henning, P; Tomlinson, L; Rigden, S P; Haycock, G B; Chantler, C

1988-01-01

The most common causes of end stage renal failure in 46 children (mean age 11 years, range 4-14) treated between January 1972 and June 1977 were: reflux nephropathy (n = 12), cystinosis (n = 7), focal and segmental glomerulosclerosis (n = 6), and Schönlein-Henoch disease (n = 5). The quality of life, degree of renal function, and height attainment of the 31 survivors were assessed in June 1985, when their mean age was 22 years (range 14-27), using hospital records and a questionnaire designed to highlight social and psychological problems. Twenty six patients had a functioning transplanted kidney. Average growth during treatment for all survivors was normal, but most were disappointed with their 'final height'. Though five patients had some form of disabling bone disease, all 31 could walk and 27 could run. Sixteen (67%) were in full or part time employment and nine were living independently. A group of 32 patients with juvenile onset diabetes treated at this hospital for at least five years were also asked to complete the questionnaire and of these, 17 responded. On average, their data could usefully be compared with those of cases of end stage renal failure. More of the diabetics had jobs, but most sexually mature patients with renal disease were concerned about their physical appearance and had not achieved any stable long term sexual relationships. We suggest that a poor body image resulting in low self esteem may be responsible for the deficiency and believe that further study in this group is warranted.

Amelioration of renal ischaemia–reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells

PubMed Central

Rogers, NM; Stephenson, MD; Kitching, AR; Horowitz, JD; Coates, PTH

2012-01-01

BACKGROUND AND PURPOSE Renal ischaemia–reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. EXPERIMENTAL APPROACH We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. KEY RESULTS Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. CONCLUSIONS AND IMPLICATIONS Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. PMID:21745189

NFκB-mediated cyclin D1 expression by microRNA-21 influences renal cancer cell proliferation.

PubMed

Bera, Amit; Ghosh-Choudhury, Nandini; Dey, Nirmalya; Das, Falguni; Kasinath, Balakuntalam S; Abboud, Hanna E; Choudhury, Goutam Ghosh

2013-12-01

MicroRNAs regulate post-transcriptomic landscape in many tumors including renal cell carcinoma. We have recently shown significantly increased expression of miR-21 in renal tumors and that this miRNA contributes to the proliferation of renal cancer cells in culture. However, the mechanism by which miR-21 regulates renal cancer cell proliferation is poorly understood. Addiction to constitutive NFκB activity is hallmark of many cancers including renal cancer. Using miR-21 Sponge in renal cancer cells to block endogenous function of miR-21, we show inhibition of phosphorylation of p65 subunit of NFκB, IKKβ and IκB, which results in attenuation of NFκB transcriptional activity. Subtle reduction in the tumor suppressor PTEN has been linked to various malignancies. We showed previously that miR-21 targeted PTEN in renal cancer cells. Inhibition of PTEN by siRNAs restored miR-21 Sponge-induced suppression of phosphorylation of p65, IKKβ, IκB and NFκB transcriptional activity along with reversal of miR-21 Sponge-reduced phosphorylation of Akt. Expression of constitutively active Akt protected against miR-21 Sponge- and PTEN-mediated decrease in p65/IKKβ/IκB phosphorylation and NFκB transcriptional activity. Furthermore, IKKβ and p65 were required for miR-21-induced renal cancer cell proliferation. Interestingly, miR-21 controlled the expression of cyclin D1 through NFκB-dependent transcription. Finally, we demonstrate that miR-21-regulated renal cancer cell proliferation is mediated by cyclin D1 and CDK4. Together, our results establish a molecular order of a phosphatase-kinase couple involving PTEN/Akt/IKKβ and NFκB-dependent cyclin D1 expression for renal carcinoma cell proliferation by increased miR-21 levels. © 2013.

NFκB-mediated cyclin D1 expression by microRNA-21 influences renal cancer cell proliferation

PubMed Central

Bera, Amit; Ghosh-Choudhury, Nandini; Dey, Nirmalya; Das, Falguni; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh

2013-01-01

MicroRNAs regulate post-transcriptomic landscape in many tumors including renal cell carcinoma. We have recently shown significantly increased expression of miR-21 in renal tumors and that this miRNA contributes to the proliferation of renal cancer cells in culture. However, the mechanism by which miR-21 regulates renal cancer cells proliferation is poorly understood. Addiction to constitutive NFκB activity is hallmark of many cancers including renal cancer. Using miR-21 Sponge in renal cancer cells to block endogenous function of miR-21, we show inhibition of phosphorylation of p65 subunit of NFκB, IKKβ and IκB, which results in attenuation of NFκB transcriptional activity. Subtle reduction in the tumor suppressor PTEN has been linked to various malignancies. We showed previously that miR-21 targeted PTEN in renal cancer cells. Inhibition of PTEN by siRNAs restored miR-21 Sponge-induced suppression of phosphorylation of p65, IKKβ, IκB and NFκB transcriptional activity along with reversal of miR-21 Sponge-reduced phosphorylation of Akt. Expression of constitutively active Akt protected against miR-21 Sponge- and PTEN-mediated decrease in p65/IKKβ/IκB phosphorylation and NFκB transcriptional activity. Furthermore, IKKβ and p65 were required for miR-21-induced renal cancer cell proliferation. Interestingly, miR-21 controlled the expression of cyclin D1 through NFκB-dependent transcription. Finally, we demonstrate that miR-21-regulated renal cancer cell proliferation is mediated by cyclin D1 and CDK4. Together, our results establish a molecular order of a phosphatase-kinase couple involving PTEN/Akt/IKKβ and NFκB-dependent cyclin D1 expression for renal carcinoma cell proliferation by increased miR-21 levels. PMID:23981302

Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

PubMed

Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

2012-05-01

Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Evaluation of renal function in patients with a main renal stone larger than 1 cm and perioperative renal functional change in minimally invasive renal stone surgery: a prospective, observational study.

PubMed

Piao, Songzhe; Park, Juhyun; Son, Hwancheol; Jeong, Hyeon; Cho, Sung Yong

2016-05-01

To compare the perioperative relative renal function and determine predictors of deterioration and recovery of separate renal function in patients with renal stones >10 mm and who underwent mini-percutaneous nephrolithotomy or retrograde intra-renal surgery. A main stone >10 mm or stones growing, high-risk stone formers and extracorporeal shock-wave lithotripsy-resistant stones were prospectively included in 148 patients. Patients with bilateral renal stones and anatomical deformities were excluded. Renal function was evaluated by estimated glomerular filtration rate, 99m-technetium dimercaptosuccinic acid and 99m-technetium diethylenetriamine pentaacetate prior to intervention and at postoperative 3 months. Logistic regression analyses were performed to find predictors of functional deterioration and recovery. The overall stone-free rate was 85.1 %. A third of patients (53/148, 35.8 %) with renal stones >10 mm showed deterioration of separate renal function. Mean renal function of operative sites showed 58.2 % (36.8 %/63.2 %) of that of contralateral sites in these patients. Abnormal separate renal function showed postoperative recovery in 31 patients (58.5 %). Three cases (5.7 %) showed deterioration of separate renal function despite no presence of remnant stones. Improvement rates of the abnormal separate renal function did not differ according to the type of surgery. The presence of hydronephrosis and three or more stones were significant predictors for renal function deterioration. Female gender and three or more stones were significantly correlated with postoperative recovery. Mini-percutaneous nephrolithotomy or retrograde intra-renal surgery was effective and safe for renal function preservation. Patients with multiple large stones should be considered for candidates of active surgical removal.

Feline chronic renal failure: clinical findings in 80 cases diagnosed between 1992 and 1995.

PubMed

Elliott, J; Barber, P J

1998-02-01

Clinical and laboratory findings at the time of first diagnosis in 80 cats with chronic renal failure (CRF) were examined in a prospective study to determine the survival time of these animals and identify possible factors contributing to the progression of feline CRF. On the basis of clinical presentation, animals were assigned to one of three groups; compensated (n = 15), uraemic (n = 39) and end-stage (n = 26) CRF. Loss of renal concentrating ability was a common finding, even before clinical signs of renal disease were evident. The plasma creatinine concentration at initial presentation was a poor predictor of survival time and the presence of significant anaemia was indicative of a poor prognosis. The study demonstrated the highly variable degree of renal impairment present at the time of diagnosis and the potentially long survival time of many compensated and uraemic cases.

A Case of Left Renal Vein Ligation in a Patient with Solitary Left Kidney Undergoing Liver Transplantation to Control Splenorenal Shunt and Improve Portal Venous Flow.

PubMed

Martino, Rodrigo B; Júnior, Eserval Rocha; Manuel, Valdano; Rocha-Santos, Vinicius; D'Albuquerque, Luis Augusto C; Andraus, Wellington

2017-10-11

BACKGROUND Adequate portal venous flow is required for successful liver transplantation. Reduced venous flow and blood flow 'steal' by collateral vessels are a concern, and when there is a prominent splenorenal shunt present, ligation of the left renal vein has been recommended to improve portal venous blood flow. CASE REPORT A 51-year-old man who had undergone right nephrectomy in childhood required liver transplantation for liver cirrhosis and hepatocellular carcinoma due to hepatitis C virus (HCV) infection. The patient had no other comorbidity and no history of hepatorenal syndrome. At transplantation surgery, portal venous flow was poor and did not improve with ligation of shunt veins, but ligation of the left renal vein improved portal venous flow. On the first and fifth postoperative days, the patient was treated with basiliximab, a chimeric monoclonal antibody to the IL-2 receptor, and methylprednisolone. The calcineurin inhibitor, tacrolimus, was introduced on the fifth postoperative day. On the sixteenth postoperative day, renal color Doppler ultrasound showed normal left renal parenchyma; hepatic Doppler ultrasound showed good portal vein flow and preserved hepatic parenchyma in the liver transplant. CONCLUSIONS This case report has shown that in a patient with a single left kidney, left renal vein ligation is feasible and safe in a patient with no other risk factors for renal impairment following liver transplantation. Modification of postoperative immunosuppression to avoid calcineurin inhibitors in the very early postoperative phase may be important in promoting good recovery of renal function and to avoid the need for postoperative renal dialysis.

Influence of CT-based depth correction of renal scintigraphy in evaluation of living kidney donors on side selection and postoperative renal function: is it necessary to know the relative renal function?

PubMed

Weinberger, Sarah; Klarholz-Pevere, Carola; Liefeldt, Lutz; Baeder, Michael; Steckhan, Nico; Friedersdorff, Frank

2018-03-22

To analyse the influence of CT-based depth correction in the assessment of split renal function in potential living kidney donors. In 116 consecutive living kidney donors preoperative split renal function was assessed using the CT-based depth correction. Influence on donor side selection and postoperative renal function of the living kidney donors were analyzed. Linear regression analysis was performed to identify predictors of postoperative renal function. A left versus right kidney depth variation of more than 1 cm was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than 5% in relative renal function after depth correction. Kidney depth variation and changes in relative renal function after depth correction would have had influence on side selection in 30 of 114 living kidney donors. CT depth correction did not improve the predictability of postoperative renal function of the living kidney donor. In general, it was not possible to predict the postoperative renal function from preoperative total and relative renal function. In multivariate linear regression analysis, age and BMI were identified as most important predictors for postoperative renal function of the living kidney donors. Our results clearly indicate that concerning the postoperative renal function of living kidney donors, the relative renal function of the donated kidney seems to be less important than other factors. A multimodal assessment with consideration of all available results including kidney size, location of the kidney and split renal function remains necessary.

UK Renal Registry 16th annual report: chapter 14 2012 multisite dialysis access audit in England, Northern Ireland and Wales and 2011 PD one year follow-up: national and centre-specific analyses.

PubMed

Briggs, Victoria; Pitcher, David; Shaw, Catriona; Fluck, Richard; Wilkie, Martin

2013-01-01

Dialysis access should be timely, minimise complications and maintain functionality. Good functional access is required for renal replacement therapy (RRT) to be successful. The aim of the combined vascular and peritoneal dialysis access audit was to examine practice patterns with respect to dialysis access and highlight variations in practice between renal centres. The UK Renal Registry collected centre-specific information on vascular and peritoneal access outcome measures including patient demographics, dialysis access type (at start of dialysis and three months after start of dialysis), surgical assessment and access functionality. The combined access audit covered incident haemodialysis (HD) and peritoneal dialysis (PD) patients in 2012 from England, Northern Ireland and Wales. Centres who had reported data on incident PD patients for the previous audit in 2011 were additionally asked to provide one year follow up data for this group. Fifty-one centres in England, Wales and Northern Ireland (representing 82% of all centres) returned data on first access from 3,720 incident HD patients and 1,018 incident PD patients. A strong relationship was seen between surgical assessment and the likelihood of starting HD with an arteriovenous fistula (AVF). Type of first access was related to the length of time known to renal services with higher numbers of AVFs and PD catheters used in patients known to renal services for at least one year. Three month and one year outcomes of HD and PD access were poorly reported. This audit provides information on important patient related outcome measures with the potential to lead to an improvement in access provision. This represents an important advance, however data collection remains suboptimal. There is wide practice variation across the England, Wales and Northern Ireland in provision of both HD and PD access which requires further exploration. © 2014 S. Karger AG, Basel.

Decreased contraction induced by endothelium-derived contracting factor in prolonged treatment of rat renal artery with endoplasmic reticulum stress inducer.

PubMed

Ando, Makoto; Matsumoto, Takayuki; Taguchi, Kumiko; Kobayashi, Tsuneo

2018-05-04

Recent evidence suggests that endoplasmic reticulum (ER) stress is involved in the regulation of various physiological functions, including those of the vascular system. However, the relationship between ER stress and vascular function is poorly understood. The endothelial cells control the vascular tone by releasing endothelium-derived relaxing factors and contracting factors (EDCFs). We hypothesized that tunicamycin, an inducer of ER stress, modifies endothelium-dependent contraction and prostaglandins (PGs), a major class of EDCFs, induced contractions in the rat renal artery in rats. An organ-culture technique was used to purely investigate the effects of ER stress on the vascular tissue. We observed that tunicamycin treatment (20 μg/mL for 23 ± 1 h) did not affect acetylcholine (ACh)-induced relaxation and decreased EDCF-mediated contractions under nitric oxide synthase (NOS) inhibition induced by ACh, ATP, or A23187 (a calcium ionophore) in the renal arteries. Under NOS inhibition, U46619 (a thromboxane A 2 mimetic)- and beraprost (a prostacyclin analog)-induced contractions were also decreased in the renal arteries of the tunicamycin-treated group (vs. vehicle), while PGE 2 - and PGF 2α -induced contractions were similar between the groups. Tunicamycin treatment slightly enhanced the contractions induced by phenylephrine, an α 1 adrenoceptor ligand. Isotonic high-K + -induced contractions were similar between the vehicle- and tunicamycin-treated groups. Another ER stress inducer, thapsigargin (4 μmol/L for 23 ± 1 h), also caused substantial reduction of ACh-induced EDCF-mediated contraction (vs. vehicle-treated group). In the cultured renal arteries, tunicamycin and thapsigargin increased the expression of binding immunoglobulin protein (BiP), an ER stress marker. In conclusion, ER stress induction directly affects renal arterial function, especially in reducing EDCF-mediated contractions.

Laparoscopic nephrectomy for giant staghorn calculus with non-functioning kidneys: Is associated unsuspected urothelial carcinoma responsible for conversion? Report of 2 cases

PubMed Central

Shah, Hemendra Navinchandra; Jain, Pritesh; Chibber, Percy Jal

2006-01-01

Background- Neglected renal stones remain a major cause of morbidity in developing countries. They not only result in functional impairment of affected kidney, but also act as an important predisposing factor for development of urothelial neoplasms. It is not uncommon to miss an associated urothelial tumor in a patient of nephrolithiasis preoperatively. Case presentation- In last 3 years, we came across two patients with giant staghorn calculus and poorly functioning kidneys who underwent laparoscopic nephrectomy. In view of significant perirenal adhesions & loss of normal tissue planes both these patients were electively converted to open surgery. The pathological examination of specimen revealed an unsuspected urothelial carcinoma in both these patients. The summary of our cases and review of literature is presented. Conclusion- It is important to keep a differential diagnosis of associated urothelial malignancy in mind in patient presenting with long standing renal calculi. The exact role of a computerized tomography and cytology in preoperative workup for detection of possible associated malignancy in such condition is yet to be defined. Similarly if laparoscopic dissection appears difficult during nephrectomy for a renal calculus with non-functional kidney, keeping a possibility of associated urothelial malignancy in mind it is advisable to dissect in a plane outside gerotas fascia as for radical nephrectomy. PMID:16398940

Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With Normal Kidney Function.

PubMed

George, Lekha K; Koshy, Santhosh K G; Molnar, Miklos Z; Thomas, Fridtjof; Lu, Jun L; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2017-08-01

Heart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes. Among 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min -1 1.73 m -2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases , Ninth Revision , diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5 mL min -1 1.73 m -2 y -1 ) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min -1 1.73 m -2 and in patients without HF were 59±14 years and 84±16 mL min -1 1.73 m -2 , respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively. HF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications. © 2017 American Heart Association, Inc.

Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1.

PubMed

Montini, Giovanni; Zucchetta, Pietro; Tomasi, Lisanna; Talenti, Enrico; Rigamonti, Waifro; Picco, Giorgio; Ballan, Alberto; Zucchini, Andrea; Serra, Laura; Canella, Vanna; Gheno, Marta; Venturoli, Andrea; Ranieri, Marco; Caddia, Valeria; Carasi, Carla; Dall'amico, Roberto; Hewitt, Ian

2009-02-01

We examined the diagnostic accuracy of routine imaging studies (ultrasonography and micturating cystography) for predicting long-term parenchymal renal damage after a first febrile urinary tract infection. This study addressed the secondary objective of a prospective trial evaluating different antibiotic regimens for the treatment of acute pyelonephritis. Data for 300 children < or =2 years of age, with normal prenatal ultrasound results, who completed the diagnostic follow-up evaluation (ultrasonography and technetium-99m-dimercaptosuccinic acid scanning within 10 days, cystography within 2 months, and repeat technetium-99m-dimercaptosuccinic acid scanning at 12 months to detect scarring) were analyzed. Outcome measures were sensitivity, specificity, and negative and positive predictive values for ultrasonography and cystography in predicting parenchymal renal damage on the 12-month technetium-99m-dimercaptosuccinic acid scans. The kidneys and urinary tracts were mostly normal. The acute technetium-99m-dimercaptosuccinic acid scans showed pyelonephritis in 54% of cases. Renal scarring developed in 15% of cases. The ultrasonographic and cystographic findings were poor predictors of long-term damage, showing minor sonographic abnormalities for 12 and reflux for 23 of the 45 children who subsequently developed scarring. The benefit of performing ultrasonography and scintigraphy in the acute phase or cystourethrography is minimal. Our findings support (1) technetium-99m-dimercaptosuccinic acid scintigraphy 6 months after infection to detect scarring that may be related to long-term hypertension, proteinuria, and renal function impairment (although the degree of scarring was generally minor and did not impair renal function) and (2) continued surveillance to identify recurrent urinary tract infections that may warrant further investigation.

Outcome of Renal Artery Reconstruction

PubMed Central

Darling, R. Clement; Kreienberg, Paul B.; Chang, Benjamin B.; Paty, Philip S. K.; Lloyd, William E.; Leather, Robert P.; Shah, Dhiraj M.

1999-01-01

Objective To evaluate the short- and long-term results of surgical reconstruction of the renal arteries, the authors review their experience with more than 600 reconstructions performed over a 12-year period. Summary Background Data Reconstruction of the renal arteries, whether for primary renal indications or concomitantly with aortic reconstruction, has evolved over the past 40 years. There is concern that renal artery reconstructions carry significant rates of mortality and morbidity and may fare poorly compared with less-invasive procedures. Methods From 1986 to 1998, 687 renal artery reconstructions were performed in 568 patients. Of these, 105 patients had simultaneous bilateral renal artery reconstructions. Fifty-six percent of the patients were male; 11% had diabetes; 35% admitted to smoking at the time of surgery. Mean age was 67 (range, 1 to 92). One hundred fifty-six (23%) were primary procedures and the remainder were adjunctive procedures with aortic reconstructions; 406 were abdominal aortic aneurysms and 125 were aortoiliac occlusive disease. Five hundred procedures were bypasses, 108 were endarterectomies, 72 were reimplantation, and 7 were patch angioplasties. There were 31 surgical deaths (elective and emergent) in the entire group for a mortality rate of 5.5%. Predictors of increased risk of death were patients with aortoiliac occlusive disease and patients undergoing bilateral simultaneous renal artery revascularization. Cause of death was primarily cardiac. Other nonfatal complications included bleeding (nine patients) and wound infection (three patients). There were 9 immediate occlusions (1.3%) and 10 late occlusions (1.5%). Thirty-three patients (4.8%) had temporary worsening of their renal function after surgery. Conclusion Renal artery revascularization is a safe and durable procedure. It can be performed in selected patients for primary renovascular pathology. It can also be an adjunct to aortic reconstruction with acceptable mortality and morbidity rates. PMID:10522722

Worsening of Renal Function During 1 Year After Hospital Discharge Is a Strong and Independent Predictor of All‐Cause Mortality in Acute Decompensated Heart Failure

PubMed Central

Ueda, Tomoya; Kawakami, Rika; Sugawara, Yu; Okada, Sadanori; Nishida, Taku; Onoue, Kenji; Soeda, Tsunenari; Okayama, Satoshi; Takeda, Yukiji; Watanabe, Makoto; Kawata, Hiroyuki; Uemura, Shiro; Saito, Yoshihiko

2014-01-01

Background Renal impairment is a common comorbidity and the strongest risk factor for poor prognosis in acute decompensated heart failure (ADHF). In clinical practice, renal function is labile during episodes of ADHF, and often worsens after discharge. The significance of worsening of renal function (WRF) after discharge has not been investigated as extensively as baseline renal function at admission or WRF during hospitalization. Methods and Results Among 611 consecutive patients with ADHF emergently admitted to our hospital, 233 patients with 3 measurements of serum creatinine (SCr) level measurements (on admission, at discharge, and 1 year after discharge) were included in the present study. Patients were divided into 2 groups according to the presence or absence of WRF at 1 year after discharge (1y‐WRF), defined as an absolute increase in SCr >0.3 mg/dL (>26.5 μmol/L) plus a ≥25% increase in SCr at 1 year after discharge compared to the SCr value at discharge. All‐cause and cardiovascular mortality were assessed as adverse outcomes. During a mean follow‐up of 35.4 months, 1y‐WRF occurred in 48 of 233 patients. There were 66 deaths from all causes. All‐cause and cardiovascular mortality were significantly higher in patients with 1y‐WRF (log‐rank P<0.0001 and P<0.0001, respectively) according to Kaplan–Meier analysis. In a multivariate Cox proportional hazards model, 1y‐WRF was a strong and independent predictor of all‐cause and cardiovascular mortality. Hemoglobin and B‐type natriuretic peptide at discharge, as well as left ventricular ejection fraction <50%, were independent predictors of 1y‐WRF. Conclusions In patients with ADHF, 1y‐WRF is a strong predictor of all‐cause and cardiovascular mortality. PMID:25370599

Worsening of renal function during 1 year after hospital discharge is a strong and independent predictor of all-cause mortality in acute decompensated heart failure.

PubMed

Ueda, Tomoya; Kawakami, Rika; Sugawara, Yu; Okada, Sadanori; Nishida, Taku; Onoue, Kenji; Soeda, Tsunenari; Okayama, Satoshi; Takeda, Yukiji; Watanabe, Makoto; Kawata, Hiroyuki; Uemura, Shiro; Saito, Yoshihiko

2014-11-04

Renal impairment is a common comorbidity and the strongest risk factor for poor prognosis in acute decompensated heart failure (ADHF). In clinical practice, renal function is labile during episodes of ADHF, and often worsens after discharge. The significance of worsening of renal function (WRF) after discharge has not been investigated as extensively as baseline renal function at admission or WRF during hospitalization. Among 611 consecutive patients with ADHF emergently admitted to our hospital, 233 patients with 3 measurements of serum creatinine (SCr) level measurements (on admission, at discharge, and 1 year after discharge) were included in the present study. Patients were divided into 2 groups according to the presence or absence of WRF at 1 year after discharge (1y-WRF), defined as an absolute increase in SCr >0.3 mg/dL (>26.5 μmol/L) plus a ≥25% increase in SCr at 1 year after discharge compared to the SCr value at discharge. All-cause and cardiovascular mortality were assessed as adverse outcomes. During a mean follow-up of 35.4 months, 1y-WRF occurred in 48 of 233 patients. There were 66 deaths from all causes. All-cause and cardiovascular mortality were significantly higher in patients with 1y-WRF (log-rank P<0.0001 and P<0.0001, respectively) according to Kaplan-Meier analysis. In a multivariate Cox proportional hazards model, 1y-WRF was a strong and independent predictor of all-cause and cardiovascular mortality. Hemoglobin and B-type natriuretic peptide at discharge, as well as left ventricular ejection fraction <50%, were independent predictors of 1y-WRF. In patients with ADHF, 1y-WRF is a strong predictor of all-cause and cardiovascular mortality. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Stent revascularization restores cortical blood flow and reverses tissue hypoxia in atherosclerotic renal artery stenosis but fails to reverse inflammatory pathways or glomerular filtration rate.

PubMed

Saad, Ahmed; Herrmann, Sandra M S; Crane, John; Glockner, James F; McKusick, Michael A; Misra, Sanjay; Eirin, Alfonso; Ebrahimi, Behzad; Lerman, Lilach O; Textor, Stephen C

2013-08-01

Atherosclerotic renal artery stenosis (ARAS) is known to reduce renal blood flow, glomerular filtration rate (GFR) and amplify kidney hypoxia, but the relationships between these factors and tubulointerstitial injury in the poststenotic kidney are poorly understood. The purpose of this study was to examine the effect of renal revascularization in ARAS on renal tissue hypoxia and renal injury. Inpatient studies were performed in patients with ARAS (n=17; >60% occlusion) before and 3 months after stent revascularization, or in patients with essential hypertension (n=32), during fixed Na(+) intake and angiotensin converting enzyme/angiotensin receptors blockers Rx. Single kidney cortical, medullary perfusion, and renal blood flow were measured using multidetector computed tomography, and GFR by iothalamate clearance. Tissue deoxyhemoglobin levels (R(2)*) were measured by blood oxygen level-dependent MRI at 3T, as was fractional kidney hypoxia (percentage of axial area with R(2)*>30/s). In addition, we measured renal vein levels of neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Pre-stent single kidney renal blood flow, perfusion, and GFR were reduced in the poststenotic kidney. Renal vein neutrophil gelatinase-associated lipocalin, tumor necrosis factor-α, monocyte chemoattractant protein-1, and fractional hypoxia were higher in untreated ARAS than in essential hypertension. After stent revascularization, fractional hypoxia fell (P<0.002) with increased cortical perfusion and blood flow, whereas GFR and neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α remained unchanged. These data demonstrate that despite reversal of renal hypoxia and partial restoration of renal blood flow after revascularization, inflammatory cytokines and injury biomarkers remained elevated and GFR failed to recover in ARAS. Restoration of vessel patency alone failed to reverse tubulointerstitial damage and partly explains the limited clinical benefit of renal stenting. These results identify potential therapeutic targets for recovery of kidney function in renovascular disease.

[Is there an age limit for cadaveric kidney donors currently?].

PubMed

Cofán Pujol, F; Oppenheimer Salinas, F; Talbot-Wright, R; Carretero González, P

1996-12-01

The insufficient number of kidney transplants has gradually raised the age limit to the cadaver kidney donor. The use of grafts harvested from older donors has been debated due to the existing structural and functional changes that might influence renal function and long-term graft survival. The foregoing aspects are discussed herein. The anatomical, histological and functional changes in the kidney associated with ageing are analyzed. The clinical experience with renal grafts from older donors before and after cyclosporine became available are reviewed. The ethical issues on whether grafts from very old donors should be used and who should receive these grafts are discussed. The use of grafts from donors over 60 years old had no significant short and medium term differences in comparison with younger donors in terms of graft survival, although a higher incidence of acute tubular necrosis and poor renal function have been observed. There are no conclusive studies on the long-term effects on graft survival when kidneys from donors aged over 65 are utilized. In our experience, the results achieved with grafts from donors over 70 has been unsatisfactory. The guidelines utilized in the selection of grafts derived from older donors are presented. Grafts from donors aged 60 to 70 may be utilized in renal transplantation following precise selection criteria. Graft survival has been satisfactory, although a higher incidence of acute tubular necrosis and higher creatinine levels have been observed. We do not advocate the use of grafts from donors over 70, except in very exceptional cases. Long-term multicenter studies on grafts from very old donors and trials using alternative immunosuppressor modalities that might permit optimal use of these grafts are warranted.

Relevance of Changes in Serum Creatinine During a Heart Failure Trial of Decongestive Strategies: Insights From the DOSE Trial

PubMed Central

BRISCO, MEREDITH A.; ZILE, MICHAEL R.; HANBERG, JENNIFER S.; WILSON, F. PERRY; PARIKH, CHIRAG R.; COCA, STEVEN G.; TANG, W.H. WILSON; TESTANI, JEFFREY M.

2017-01-01

Background Worsening renal function (WRF) is a common endpoint in decompensated heart failure clinical trials because of associations between WRF and adverse outcomes. However, WRF has not universally been identified as a poor prognostic sign, challenging the validity of WRF as a surrogate endpoint. Our aim was to describe the associations between changes in creatinine and adverse outcomes in a clinical trial of decongestive therapies. Methods and Results We investigated the association between changes in creatinine and the composite endpoint of death, rehospitalization or emergency room visit within 60 days in 301 patients in the Diuretic Optimization Strategies Evaluation (DOSE) trial. WRF was defined as an increase in creatinine >0.3 mg/dL and improvement in renal function (IRF) as a decrease >0.3 mg/dL. When examining linear changes in creatinine from baseline to 72 hours (the coprimary endpoint of DOSE), increasing creatinine was associated with lower risk for the composite outcome (HR = 0.81 per 0.3 mg/dL increase, 95% CI 0.67–0.98, P = .026). Compared with patients with stable renal function (n = 219), WRF (n = 54) was not associated with the composite endpoint (HR = 1.17, 95% CI = 0.77–1.78, P = .47). However, compared with stable renal function, there was a strong relationship between IRF (n = 28) and the composite endpoint (HR = 2.52, 95% CI = 1.57–4.03, P <.001). Conclusion The coprimary endpoint of the DOSE trial, a linear increase in creatinine, was paradoxically associated with improved outcomes. This was driven by absence of risk attributable to WRF and a strong risk associated with IRF. These results argue against using changes in serum creatinine as a surrogate endpoint in trials of decongestive strategies. PMID:27374839

Predicting postnatal renal function of prenatally detected posterior urethral valves using fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient determination.

PubMed

Faure, Alice; Panait, Nicoleta; Panuel, Michel; Alessandrini, Pierre; D'Ercole, Claude; Chaumoitre, Kathia; Merrot, Thierry

2017-07-01

The objective of this study was to evaluate the accuracy of fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) determination to predict postnatal renal function (nadir creatinine at 1 year and eGFR) of men with posterior urethral valves (PUV). Between 2003 and 2014, 11 MRI were performed on fetuses (between 28 and 32 weeks) in whom second trimester sonography suggested severe bilateral urinary tract anomalies, suspected of PUV. The ADC of the 11 fetuses ranged from 1.3 to 2.86 mm 2  s -1 (median = 1.79 mm 2  s -1 , normal range for fetal kidney: 1.1-1.8). Two pregnancies with ADC > 2.6 mm 2  s -1 were interrupted; the autopsy confirmed PUV and Potter syndrome. For the remaining nine babies, the follow-up was 5.4 years (0.8-10). Four children with abnormal ADC (1.8-2.3) had chronic kidney disease. The remaining five cases with normal nadir creatinine and eGFR had normal ADC. One case with unilateral elevated ADC had a poor ipsilateral renal function on dimercaptosuccinic acid scan. Here, it seems that diffusion-weighted magnetic resonance imaging with ADC determination could be useful in accurately evaluating fetal kidneys in PUV and predicting renal function. It may be an additional, non-invasive method when biologic and sonographic findings are inconclusive, especially in the case of oligohydramnios. Further studies are needed to confirm our data. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Chronic kidney disease and poor outcomes in ischemic stroke: is impaired cerebral autoregulation the missing link?

PubMed

Castro, Pedro; Azevedo, Elsa; Rocha, Isabel; Sorond, Farzaneh; Serrador, Jorge M

2018-03-02

Chronic kidney disease increases stroke incidence and severity but the mechanisms behind this cerebro-renal interaction are mostly unexplored. Since both vascular beds share similar features, microvascular dysfunction could be the possible missing link. Therefore, we examined the relationship between renal function and cerebral autoregulation in the early hours post ischemia and its impact on outcome. We enrolled 46 ischemic strokes (middle cerebral artery). Dynamic cerebral autoregulation was assessed by transfer function (coherence, phase and gain) of spontaneous blood pressure oscillations to blood flow velocity within 6 h from symptom-onset. Estimated glomerular filtration rate (eGFR) was calculated. Hemorrhagic transformation (HT) and white matter lesions (WML) were collected from computed tomography performed at presentation and 24 h. Outcome was evaluated with modified Rankin Scale at 3 months. High gain (less effective autoregulation) was correlated with lower eGFR irrespective of infarct side (p < 0.05). Both lower eGFR and higher gain correlated with WML grade (p < 0.05). Lower eGFR and increased gain, alone and in combination, progressively reduced the odds of a good functional outcome [ipsilateral OR = 4.39 (CI95% 3.15-25.6), p = 0.019; contralateral OR = 8.15 (CI95% 4.15-15.6), p = 0.002] and increased risk of HT [ipsilateral OR = 3.48 (CI95% 0.60-24.0), p = 0.132; contralateral OR = 6.43 (CI95% 1.40-32.1), p = 0.034]. Lower renal function correlates with less effective dynamic cerebral autoregulation in acute ischemic stroke, both predicting a bad outcome. The evaluation of serum biomarkers of renal dysfunction could have interest in the future for assessing cerebral microvascular risk and relationship with stroke complications.

Kidney disease in heart failure: the importance of novel biomarkers for type 1 cardio-renal syndrome detection.

PubMed

Palazzuoli, Alberto; McCullough, Peter A; Ronco, Claudio; Nuti, Ranuccio

2015-08-01

Chronic kidney disease (CKD) in heart failure (HF) has been recognized as an independent risk factor for adverse outcome, although the most important clinical trials tend to exclude patients with moderate and severe renal insufficiency. Despite this common association, the precise pathophysiological connection and liaison between heart and kidney is partially understood. Moreover, is it not enough considering how much cardio-renal syndrome type 1 is attributable to previous CKD, and how much to new-onset acute kidney injury (AKI). Neither development of AKI, its progression and time nor duration is related to an adverse outcome. An AKI definition is not universally recognized, and many confounding terms have been used in literature: "worsening renal function", "renal impairment", "renal dysfunction", etc., are all names that contribute to misunderstanding, and do not facilitate an universal classification. Therefore, AKI development should be the consequence of the basal clinical characteristics of patients, different primitive kidney disease and hemodynamic status. AKI could also be the mirror of several underlying associated diseases poorly controlled. Finally, it is not clear which is the optimal laboratory tool for identifying patients with an increased risk of AKI. In the current report, we review the different kidney diseases' impact in HF, and we analyze the modalities for AKI recognition during HF focusing our attention about some new biomarkers with potential application in the current setting.

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis*

PubMed Central

Wu, Tianfu; Du, Yong; Han, Jie; Singh, Sandeep; Xie, Chun; Guo, Yuyuan; Zhou, Xin J.; Ahn, Chul; Saxena, Ramesh; Mohan, Chandra

2013-01-01

There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ∼280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation. The significant elevation in urinary angiostatin was next validated in an independent cohort of SLE patients (n = 100) using ELISA. Among patients with SLE, urine angiostatin was significantly increased in active SLE compared with inactive SLE, correlating well with the SLEDAI disease activity index and SLICC renal activity score (r = 0.66, p < 0.0001). ROC curve analysis further confirmed that urinary angiostatin had the capacity to discriminate patients with active SLE from those with inactive disease. Patients with Class IV lupus nephritis exhibited the highest levels of urinary angiostatin. Immunohistochemistry staining localized angiostatin expression to the renal tubular cells in these patients. Finally, when paired urine-kidney samples procured concurrently from patients with LN were next examined, urine angiostatin levels correlated strongly with the renal pathology chronicity index, but not with the activity index. Given that Class IV lupus nephritis and renal pathology chronicity changes forebode poor renal and patient survival, urinary angiostatin emerges as a novel noninvasive marker of renal disease in SLE. Longitudinal studies are in progress to further assess the disease-predictive potential of urinary angiostatin. PMID:23345539

Rhabdomyolysis case based on hypothyroidism

PubMed Central

Katipoglu, Bilal; Acehan, Fatih; Meteris, Ayşenur; Yılmaz, Nisbet

2016-01-01

Summary Hypothyroidism is a wide clinical spectrum disorder and only a few cases in literature show this. Rhabdomyolysis and acute renal impairment can be seen concurrently in a hypothyroid state. We report a case of severe hypothyroidism with poor drug compliance leading to rhabdomyolysis and acute kidney injury. Learning points: Hypothyroidism is a rare cause of acute kidney injury. In this case report, we studied a rare occurrence of acute renal impairment due to hypothyroidism with poor drug compliance, which induced rhabdomyolysis. Our report emphasized that thyroid status should be evaluated in patients with unexplained acute renal impairment or presenting with the symptoms of muscle involvement. PMID:27855234

Inappropriate Prescription and Renal Function Among Older Patients with Cognitive Impairment.

PubMed

Sönnerstam, Eva; Sjölander, Maria; Gustafsson, Maria

2016-12-01

Older people are more sensitive to drugs and adverse drug reactions than younger people because of age-related physiological changes such as impaired renal function. As people with dementia are particularly vulnerable to the effects of drugs, it is especially important to evaluate the dosages of renally cleared medications in this group. The aim of this study was to estimate the prevalence of impaired renal function and inappropriate prescriptions on the basis of renal function among older patients with dementia or cognitive impairment. The medical records of 428 patients aged ≥65 years who were admitted to two hospitals in northern Sweden were reviewed and renally cleared medications were identified. The Cockcroft-Gault equation was used to evaluate renal function. Doses were evaluated according to the Geriatric Dosage Handbook. Renal function was impaired (estimated glomerular filtration rate <60 ml/min) in 65.4 % of the study population. Impaired renal function was associated with increasing age. Among 547 prescriptions identified as renally cleared medications, 9.1 % were inappropriate based on the patient's renal function; 13.5 % of the 326 patients prescribed renally cleared medications had inappropriate prescriptions. Inappropriate prescriptions were more common among patients living in nursing homes. Impaired renal function is common and inappropriate prescription is prevalent among old people with cognitive impairment in northern Sweden. Continuous consideration of renal function is important when prescribing medications to this group.

Clinical application of calculated split renal volume using computed tomography-based renal volumetry after partial nephrectomy: Correlation with technetium-99m dimercaptosuccinic acid renal scan data.

PubMed

Lee, Chan Ho; Park, Young Joo; Ku, Ja Yoon; Ha, Hong Koo

2017-06-01

To evaluate the clinical application of computed tomography-based measurement of renal cortical volume and split renal volume as a single tool to assess the anatomy and renal function in patients with renal tumors before and after partial nephrectomy, and to compare the findings with technetium-99m dimercaptosuccinic acid renal scan. The data of 51 patients with a unilateral renal tumor managed by partial nephrectomy were retrospectively analyzed. The renal cortical volume of tumor-bearing and contralateral kidneys was measured using ImageJ software. Split estimated glomerular filtration rate and split renal volume calculated using this renal cortical volume were compared with the split renal function measured with technetium-99m dimercaptosuccinic acid renal scan. A strong correlation between split renal function and split renal volume of the tumor-bearing kidney was observed before and after surgery (r = 0.89, P < 0.001 and r = 0.94, P < 0.001). The preoperative and postoperative split estimated glomerular filtration rate of the operated kidney showed a moderate correlation with split renal function (r = 0.39, P = 0.004 and r = 0.49, P < 0.001). The correlation between reductions in split renal function and split renal volume of the operated kidney (r = 0.87, P < 0.001) was stronger than that between split renal function and percent reduction in split estimated glomerular filtration rate (r = 0.64, P < 0.001). The split renal volume calculated using computed tomography-based renal volumetry had a strong correlation with the split renal function measured using technetium-99m dimercaptosuccinic acid renal scan. Computed tomography-based split renal volume measurement before and after partial nephrectomy can be used as a single modality for anatomical and functional assessment of the tumor-bearing kidney. © 2017 The Japanese Urological Association.

MicroRNA profiling of human kidney cancer subtypes.

PubMed

Petillo, David; Kort, Eric J; Anema, John; Furge, Kyle A; Yang, Ximing J; Teh, Bin Tean

2009-07-01

Although the functions of most of the identified microRNAs (miRNAs) have yet to be determined, their use as potential biomarkers has been considered in several human diseases and cancers. In order to understand their role in renal tumorigenesis, we screened the expression levels of miRNAs in four subtypes of human renal neoplasms: clear cell, papillary, and chromophobe renal cell carcinomas (RCC) as well as benign renal oncocytomas. We found a unique miRNA signature for each subtype of renal tumor. Furthermore, we identified unique patterns of miRNA expression distinguishing clear cell RCC cases with favorable vs. unfavorable outcome. Specifically, we documented the overexpression of miRs 424 and 203 in clear cell RCC relative to papillary RCC, as well as the inversion of expression of miR-203 in the benign oncocytomas (where it is underexpressed relative to normal kidney) as compared to the malignant chromophobe RCC (where it is overexpressed relative to normal kidney). Our results further suggest that overexpression of S-has-miR-32 is associated with poor outcome. While previous studies have identified unique miRNA expression pattern distinguishing tumors from different anatomical locations, here we extend this principle to demonstrate the utility of miRNA expression profiling to identify a signature unique to various tumor subtypes at a single anatomic locus.

Cardiovascular risk profile and frailty in a population-based study of older British men.

PubMed

Ramsay, S E; Arianayagam, D S; Whincup, P H; Lennon, L T; Cryer, J; Papacosta, A O; Iliffe, S; Wannamethee, S G

2015-04-01

Frailty in older age is known to be associated with cardiovascular disease (CVD) risk. However, the extent to which frailty is associated with the CVD risk profile has been little studied. Our aim was to examine the associations of a range of cardiovascular risk factors with frailty and to assess whether these are independent of established CVD. Cross-sectional study of a socially representative sample of 1622 surviving men aged 71-92 examined in 2010-2012 across 24 British towns, from a prospective study initiated in 1978-1980. Frailty was defined using the Fried phenotype, including weight loss, grip strength, exhaustion, slowness and low physical activity. Among 1622 men, 303 (19%) were frail and 876 (54%) were pre-frail. Compared with non-frail, those with frailty had a higher odds of obesity (OR 2.03, 95% CI 1.38 to 2.99), high waist circumference (OR 2.30, 95% CI 1.67 to 3.17), low high-density lipoprotein-cholesterol (HDL-C) (OR 2.28, 95% CI 1.47 to 3.54) and hypertension (OR 1.79, 95% CI 1.27 to 2.54). Prevalence of these factors was also higher in those with frailty (prevalence in frail vs non-frail groups was 46% vs 31% for high waist circumference, 20% vs 11% for low HDL and 78% vs 65% for hypertension). Frail individuals had a worse cardiovascular risk profile with an increased risk of high heart rate, poor lung function (forced expiratory volume in 1 s (FEV1)), raised white cell count (WCC), poor renal function (low estimated glomerular filtration rate), low alanine transaminase and low serum sodium. Some risk factors (HDL-C, hypertension, WCC, FEV1, renal function and albumin) were also associated with being pre-frail. These associations remained when men with prevalent CVD were excluded. Frailty was associated with increased risk of a range of cardiovascular factors (including obesity, HDL-C, hypertension, heart rate, lung function, renal function) in older people; these associations were independent of established CVD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

PubMed

DiBona, Gerald F

2005-03-01

Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

Inflammation and metabolic disorders.

PubMed

Navab, Mohamad; Gharavi, Nima; Watson, Andrew D

2008-07-01

Poor nutrition, overweight and obesity have increasingly become a public health concern as they affect many metabolic disorders, including heart disease, diabetes, digestive system disorders, and renal failure. Study of the effects of life style including healthy nutrition will help further elucidate the mechanisms involved in the adverse effects of poor nutrition. Unhealthy life style including poor nutrition can result in imbalance in our oxidation/redox systems. Lipids can undergo oxidative modification by lipoxygenases, cyclooxygenases, myeloperoxidase, and other enzymes. Oxidized phospholipids can induce inflammatory molecules in the liver and other organs. This can contribute to inflammation, leading to coronary heart disease, stroke, renal failure, inflammatory bowl disease, metabolic syndrome, bone and joint disorders, and even certain types of cancer. Our antioxidant and antiinflammatory defense mechanisms contribute to a balance between the stimulators and the inhibitors of inflammation. Beyond a point, however, these systems might be overwhelmed and eventually fail. High-density lipoprotein is a potent inhibitor of the formation of toxic oxidized lipids. High-density lipoprotein is also an effective system for stimulating the genes whose products are active in the removal, inactivation, and elimination of toxic lipids. Supporting the high-density lipoprotein function should help maintain the balance in these systems. It is hoped that the present report would elucidate some of the ongoing work toward this goal.

Effects of adding Rheum officinale to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on renal function in patients with chronic renal failure: A meta-analysis of randomized controlled trials
.

PubMed

Yang, Yue; Ma, Ye-Ping; Zhang, Zheng; Dai, Pei-Lin; Li, Ping; Li, Wen-Ge

2018-06-01

Rheum officinale is a traditional medicinal herb used widely in China to treat chronic renal failure, but the proof of evidence-based medicine is poor. This meta-analysis aims to assess the benefits of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) supplemented with Rheum officinale for delaying the progression of chronic renal failure. The MEDLINE, EMBASE, Cochrane Library, SinoMed, Chinese National Knowledge Infrastructure, Wanfang, and VIP databases were searched to identify studies published before September 2016 that investigated the effects of ACEI/ARB plus the Chinese patented medicine Rheum (CPM-Rheum) compared to ACEI/ARB alone in lowering serum creatinine (SCr) and blood urea nitrogen (BUN) levels in chronic renal failure patients. Review Manager 5.3 was used to perform the meta-analysis. Fixed- and random-effects models were used to analyze the data. The meta-analysis included nine clinical trials. Comparisons of patients before and after treatment with ACEI/ARB plus CPM-Rheum or ACEI/ARB alone revealed that ACEI/ARB plus CPM-Rheum resulted in significantly greater reductions in SCr (short-term: weighted mean difference (WMD): 17.26, 95% confidence interval (CI): 7.28 - 27.24; long-term: WMD: 63.71, 95% CI: 51.01 - 76.41) and BUN (short-term: WMD: 1.70, 95% CI: 1.27 - 2.12; long-term: WMD: 3.98, 95% CI: 3.14 - 4.82) than ACEI/ARB alone. In patients with chronic renal failure, the addition of CPM-Rheum to ACEI/ARB significantly lowered both SCr and BUN, particularly after long-term administration. Thus, the combination of ACEI/ARB and CPM-Rheum may improve the treatment of patients with impaired renal function.
.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mann, S.J.; Pickering, T.G.; Sos, T.A.

The purpose of this study was to determine the sensitivity, specificity, and clinical usefulness of renography performed in combination with captopril administration (captopril renography) in diagnosing renal artery stenosis. Fifty-five patients with suspected renal artery stenosis underwent renography prior to performance of renal angiography. Renography was performed on two consecutive days using technetium-99m-diethylenetiamine pentaacetic acid (DTPA) as an index of glomerular filtration rate and iodine-131-orthoiodohippurate (OIH) as an index of renal blood flow. Captopril (25 mg orally, crushed) was administered 1 hour before the second study. Renal artery stenosis was defined as a stenosis exceeding 70%. Renographic criteria were thenmore » established, retrospectively, to differentiate renal artery stenosis from essential hypertension based on (1) asymmetry of function and (2) the presence of captopril-induced changes. Renal artery stenosis was detected in 35 of 55 patients (21 with unilateral and 14 with bilateral stenosis). Three criteria were established for diagnosing renal artery stenosis: (1) a percent uptake of DTPA by the affected kidney of less than 40% of the combined bilateral uptake, (2) a delayed time to peak uptake of DTPA, which was more than 5 minutes longer in the affected kidney than in the contralateral kidney, (3) a delayed excretion of DTPA, with retention at 15 minutes, as a fraction of peak activity, more than 20% greater than in the contralateral kidney. The presence of one or more of these criteria was diagnostic of renal artery stenosis, with a sensitivity and specificity of 71% and 75%, respectively before captopril administration, and 94% and 95% after captopril administration. Lesser degrees of asymmetry (i.e., uptake of 40% to 50%) had very poor diagnostic specificity.« less

Percutaneous renal sympathetic nerve ablation for loin pain haematuria syndrome.

PubMed

Gambaro, Giovanni; Fulignati, Pierluigi; Spinelli, Alessio; Rovella, Valentina; Di Daniele, Nicola

2013-09-01

Loin pain haematuria syndrome (LPHS) is a severe renal pain condition of uncertain origin and often resistant to treatment. Nephrectomy and renal autotrasplantation have occasionally been performed in very severe cases. Its pathogenesis is controversial. A 40-year-old hypertensive lady was diagnosed with LPHS after repeated diagnostic imaging procedures had ruled out any renal, abdominal or spinal conditions to justify pain. Notwithstanding treatment with three drugs, she had frequent hypertensive crises during which the loin pain was dramatically exacerbated. Vascular causes of the pain and hypertension were investigated and excluded. Her renal function was normal. The patient was referred to a multidisciplinary pain clinic, but had no significant improvement in her pain symptoms despite the use of non-steroidal anti-inflammatory drugs, adjuvant antidepressants and opioid-like agents. The pain and the discomfort were so severe that her quality of life was very poor, and her social and professional activities were compromised. Nephrectomy and renal autotransplantation have occasionally been performed in these cases. Since visceral pain signals flow through afferent sympathetic fibres, we felt that percutaneous catheter-based radiofrequency ablation of the renal sympathetic nerve fibres (recently introduced for the treatment of drug-resistant hypertension) could be valuable for pain relief. We treated the patient with radiofrequency ablation (Medtronic Symplicity Catheter) applied only to the right renal artery. After a 6-month follow-up, the patient is pain free and normotensive with all drugs withdrawn. She has experienced no hypertensive crises in the meantime. This observation suggests that percutaneous sympathetic denervation could prove to be an effective mini-invasive strategy for the treatment of chronic renal pain, and LPHS in particular.

Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in patients with chronic heart failure.

PubMed

Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Funayama, Akira; Kinoshita, Daisuke; Yokoyama, Miyuki; Takahashi, Tetsuya; Nishiyama, Satoshi; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

2016-02-01

Renal tubular damage (RTD) and hypoalbuminemia are risks for poor prognosis in patients with chronic heart failure (CHF). Renal tubules play a pivotal role in amino acid and albumin reabsorption, which maintain serum albumin levels. The aims of the present study were to (1) examine the association of RTD with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD and hypoalbuminemia in patients with CHF. We measured N-acetyl-β-D-glucosamidase (NAG) levels and the urinary β2-microglobulin to creatinine ratio (UBCR) in 456 patients with CHF. RTD was defined as UBCR ≥ 300 μg/g or NAG ≥ 14.2 U/g. There were moderate correlations between RTD markers and serum albumin (NAG, r = -0.428, P < 0.0001; UBCR, r = -0.399, P < 0.0001). Multivariate logistic analysis showed that RTD was significantly related to hypoalbuminemia in patients with CHF. There were 134 cardiac events during a median period of 808 days. The comorbidity of RTD and hypoalbuminemia was increased with advancing New York Heart Association functional class. Multivariate Cox proportional hazard regression analysis showed that the presence of RTD and hypoalbuminemia was associated with cardiac events. The net reclassification index was significantly improved by adding RTD and hypoalbuminemia to the basic risk factors. Comorbid RTD and hypoalbuminemia are frequently observed and increase the risk for extremely poor outcome in patients with CHF.

Inactivation of bone morphogenetic protein 2 may predict clinical outcome and poor overall survival for renal cell carcinoma through epigenetic pathways

PubMed Central

Mitsui, Yozo; Hirata, Hiroshi; Arichi, Naoko; Hiraki, Miho; Yasumoto, Hiroaki; Chang, Inik; Fukuhara, Shinichiro; Yamamura, Soichiro; Shahryari, Varahram; Deng, Guoren; Saini, Sharanjot; Majid, Shahana; Dahiya, Rajvir; Tanaka, Yuichiro; Shiina, Hiroaki

2015-01-01

We investigated whether impaired regulation of bone morphogenetic protein-2 (BMP-2) via epigenetic pathways is associated with renal cell carcinoma (RCC) pathogenesis. Expression and CpG methylation of the BMP-2 gene were analyzed using RCC cell lines, and 96 matched RCC and normal renal tissues. We also performed functional analysis using BMP-2 restored RCC cells. A significant association of BMP-2 mRNA expression was also found with advanced tumor stage and lymph node involvement, while lower BMP-2 mRNA expression was significantly associated with poor overall survival after radical nephrectomy. In RCC cells, BMP-2 restoration significantly inhibited cell proliferation, migration, invasion, and colony formation. In addition, BMP-2 overexpression induced p21WAF1/CIP1 and p27KIP1 expression, and cellular apoptosis in RCC cells. BMP-2 mRNA expression was significantly enhanced in RCC cells by 5-aza-2′-deoxycitidine treatment. The prevalence of BMP-2 promoter methylation was significantly greater and BMP-2 mRNA expression was significantly lower in RCC samples as compared to normal kidney samples. Furthermore, a significant correlation was found between BMP-2 promoter methylation and mRNA transcription in tumors. Aberrant BMP-2 methylation and the resultant loss of BMP-2 expression may be a useful molecular marker for designing improved diagnostic and therapeutic strategies for RCC. PMID:25797254

Predictors of Recoverability of Renal Function after Pyeloplasty in Adults with Ureteropelvic Junction Obstruction.

PubMed

Li, Xiao-Dong; Wu, Yu-Peng; Wei, Yong; Chen, Shao-Hao; Zheng, Qing-Shui; Cai, Hai; Xue, Xue-Yi; Xu, Ning

2018-01-01

This study aimed to identify factors predicting the recoverability of renal function after pyeloplasty in adult patients with ureteropelvic junction obstruction. We retrospectively reviewed 138 adults with unilateral renal obstruction-induced hydronephrosis and who underwent Anderson-Hynes dismembered pyeloplasty from January 2013 to January 2016. Hydronephrosis was classified preoperatively according to the Society for Fetal Urology (SFU) grading system. All patients underwent Doppler ultrasonography, excretory urography, computed tomography, and technetium-99m-diethylenetriamine pentaacetic acid radioisotope (99mTc DTPA) renography before and after surgery. Renal resistive index (RRI) and 99mTc DTPA renography were repeated at 1, 3, 6, and 12 months. Multivariate analysis identified age, renal pelvic type, SFU grade, preoperative RRI, decline of RRI, and renal parenchyma to hydronephrosis area ratio (PHAR) as independent predictors of renal function recoverability after pyeloplasty. However, preoperative RRI and RRI decline were not significantly associated with recoverability of renal function in patients aged >35 years. Lower preoperative RRI, greater decline in RRI, higher PHAR, lower SFU grade, and extrarenal pelvis were associated with greater improvements in postoperative renal function. Preoperative differential renal function cannot independently predict the recoverability of postoperative renal function in adult patients with unilateral renal obstruction-induced hydronephrosis. SFU grade, renal pelvic type, PHAR, preoperative RRI, and decline in RRI were significantly associated with the recoverability of renal function in adult patients aged <35 years, while only SFU grade, renal pelvic type, and PHAR were significantly associated with renal function recoverability in patients aged ≥35 years. Renal function recovery was better in patients younger than 35 years when compared with older patients. © 2018 S. Karger AG, Basel.

Renal dopamine containing nerves. What is their functional significance?

PubMed

DiBona, G F

1990-06-01

Biochemical and morphological studies indicate that there are nerves within the kidney that contain dopamine and that various structures within the kidney contain dopamine receptors. However, the functional significance of these renal dopamine containing nerves in relation to renal dopamine receptors is unknown. The functional significance could be defined by demonstrating that an alteration in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves is dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors. Thus, the hypothesis becomes: reflex or electrical activation of efferent renal nerves causes alterations in renal function (eg, renal blood flow, water and solute handling) that are inhibited by specific and selective dopamine receptor antagonists. As reviewed herein, the published experimental data do not support the hypothesis. Therefore, the view that alterations in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves are dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors remains unproven.

Case study: the link between hypertension and diabetes.

PubMed

Bakris, George L; Gonzalez, Edgar R

2007-06-01

Many diabetics develop hypertension, and it is a major risk factor for cardiovascular and microvascular complications. To review a case study of a patient with poorly controlled hypertension and diabetes. Further assessment of this case study shows that the patient has poorly controlled hypertension, despite multiple medications. The patient also has metabolic syndrome complicated.by diabetes, microalbuminuria and peripheral arterial disease. The patient's hypertensive treatment options must be evaluated in light of the fact that polypharmacy has made it more difficult for her to achieve glycemic control. A panoply of drugs and drug classes are available from which to choose: diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone antagonists. New vasodilatory betablockers reduce adverse drug reactions and produce beneficial effects on arterial vasculature. Various beta~blockers' effects on insulin sensitivity are compared. Older beta-blockers have been shown to have detrimental effects on glucose or lipid parameters. Newer agents such as nebivolol do not impact lipid, glucose, insulin, or high-density lipoproteins. Instead, nebivolol stimulates endothelial nitric oxide release in renal arteries and improves renal function.

Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

PubMed Central

Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-01

Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

Association between pulmonary function and renal function: findings from China and Australia.

PubMed

Yu, Dahai; Chen, Tao; Cai, Yamei; Zhao, Zhanzheng; Simmons, David

2017-05-01

The relationship between obstructive lung function and impaired renal function is unclear. This study investigated the dose-response relationship between obstructive lung function and impaired renal function. Two independent cross-sectional studies with representative sampling were applied. 1454 adults from rural Victoria, Australia (1298 with normal renal function, 156 with impaired renal function) and 5824 adults from Nanjing, China (4313 with normal renal function, 1511 with impaired renal function). Pulmonary function measurements included forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Estimated glomerular filtration rate (eGFR), and impaired renal function marked by eGFR <60 mL/min/1.73m 2 were used as outcome. eGFR increased linearly with FEV1 in Chinese participants and with FVC in Australians. A non-linear relationship with peaked eGFR was found for FEV1 at 2.65 L among Australians and for FVC at 2.78 L among Chinese participants, respectively. A non-linear relationship with peaked eGFR was found for the predicted percentage value of forced expiratory volume in 1 s (PFEV1) at 81-82% and for the predicted percentage value of forced vital capacity (PFVC) at 83-84% among both Chinese and Australian participants, respectively. The non-linear dose-response relationships between lung capacity measurements (both for FEV1 and FVC) and risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 3.05 L both for FEV1 and FVC, respectively. The non-linear relationship between PFEV and PVC and the risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 76-77% for PFEV1 and 79-80% for PFVC, respectively. In both Australian and Chinese populations, the risk of impaired renal function increased both with FEV1 and FVC below 3.05 L, with PFEV1 below 76-77% or with PFVC below 79-80%, respectively. Obstructive lung function was associated with increased risk of reduced renal function. The screen for impaired renal function in patients with obstructive lung disease might be useful to ensure there was no impaired renal function before the commencement of potentially nephrotoxic medication where indicated (eg diuretics).

Bidirectional relationship between renal function and periodontal disease in older Japanese women.

PubMed

Yoshihara, Akihiro; Iwasaki, Masanori; Miyazaki, Hideo; Nakamura, Kazutoshi

2016-09-01

The purpose of this study was to evaluate the reciprocal effects of chronic kidney disease (CKD) and periodontal disease. A total of 332 postmenopausal never smoking women were enrolled, and their serum high-sensitivity C-reactive protein, serum osteocalcin and serum cystatin C levels were measured. Poor renal function was defined as serum cystatin C > 0.91 mg/l. Periodontal disease markers, including clinical attachment level and the periodontal inflamed surface area (PISA), were also evaluated. Logistic regression analysis was conducted to evaluate the relationships between renal function and periodontal disease markers, serum osteocalcin level and hsCRP level. The prevalence-rate ratios (PRRs) on multiple Poisson regression analyses were determined to evaluate the relationships between periodontal disease markers and serum osteocalcin, serum cystatin C and serum hsCRP levels. On logistic regression analysis, PISA was significantly associated with serum cystatin C level. The odds ratio for serum cystatin C level was 2.44 (p = 0.011). The PRR between serum cystatin C level and periodontal disease markers such as number of sites with clinical attachment level ≥6 mm was significantly positive (3.12, p < 0.001). Similar tendencies were shown for serum osteocalcin level. This study suggests that CKD and periodontal disease can have reciprocal effects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neutrophil-to-lymphocyte ratio as a predictor of worsening renal function in diabetic patients (3-year follow-up study).

PubMed

Azab, Basem; Daoud, Jacques; Naeem, Fahad Ben; Nasr, Rabih; Ross, Jennifer; Ghimire, Pratima; Siddiqui, Ayesha; Azzi, Nadine; Rihana, Nancy; Abdallah, Marie; Azzi, Nassif; Patel, Parishram; Kleiner, Morton; El-Sayegh, Suzanne

2012-01-01

Previous studies have demonstrated the role of inflammation in diabetic nephropathy (DN). Neutrophil to lymphocyte ratio (NLR) rather than other white cell parameters was found to be a useful inflammatory marker to predict adverse outcomes in medical and surgical conditions. Nevertheless, the value of NLR in predicting DN has not been elucidated. An observational study included 338 diabetic patients, who were followed at our clinic between 2007 and 2009. We arranged our patients into tertiles according to their 2007 NLR. The primary outcome was continuous decrease of GFR >12 mL/min between 2007 and 2009 with the last GFR <60 mL/min. The lowest NLR tertile had fewer patients (2.7%) with primary outcome (i.e., worsening renal function) compared with middle and highest NLR tertiles, which had more patients with primary outcomes (8.7% and 11.5%, respectively) with a significant p-value 0.0164. When other potential confounders were individually analyzed with NLR tertile, the NLR tertiles remained a significant predictor of poor GFR outcome in the presence of other variables (hemoglobin A1C, systolic blood pressure, diastolic blood pressure, age, and congestive heart failure with p-values 0.018, 0.019, 0.017, 0.033, and 0.022, respectively). NLR predicted the worsening of the renal function in diabetic patients. Further studies are needed to confirm this result.

Renal Function Descriptors in Neonates: Which Creatinine-Based Formula Best Describes Vancomycin Clearance?

PubMed

Bhongsatiern, Jiraganya; Stockmann, Chris; Yu, Tian; Constance, Jonathan E; Moorthy, Ganesh; Spigarelli, Michael G; Desai, Pankaj B; Sherwin, Catherine M T

2016-05-01

Growth and maturational changes have been identified as significant covariates in describing variability in clearance of renally excreted drugs such as vancomycin. Because of immaturity of clearance mechanisms, quantification of renal function in neonates is of importance. Several serum creatinine (SCr)-based renal function descriptors have been developed in adults and children, but none are selectively derived for neonates. This review summarizes development of the neonatal kidney and discusses assessment of the renal function regarding estimation of glomerular filtration rate using renal function descriptors. Furthermore, identification of the renal function descriptors that best describe the variability of vancomycin clearance was performed in a sample study of a septic neonatal cohort. Population pharmacokinetic models were developed applying a combination of age-weight, renal function descriptors, or SCr alone. In addition to age and weight, SCr or renal function descriptors significantly reduced variability of vancomycin clearance. The population pharmacokinetic models with Léger and modified Schwartz formulas were selected as the optimal final models, although the other renal function descriptors and SCr provided reasonably good fit to the data, suggesting further evaluation of the final models using external data sets and cross validation. The present study supports incorporation of renal function descriptors in the estimation of vancomycin clearance in neonates. © 2015, The American College of Clinical Pharmacology.

Management of metastatic renal cell carcinoma patients with poor-risk features: current status and future perspectives.

PubMed

Santoni, Matteo; De Tursi, Michele; Felici, Alessandra; Lo Re, Giovanni; Ricotta, Riccardo; Ruggeri, Enzo Maria; Sabbatini, Roberto; Santini, Daniele; Vaccaro, Vanja; Milella, Michele

2013-06-01

With seven agents approved for renal cell carcinoma within the past few years, there has undoubtedly been progress in treating this disease. However, patients with poor-risk features remain a challenging and difficult-to-treat population, with the mTOR inhibitor, temsirolimus, the only agent approved in the first-line setting. Phase III trial data are still lacking VEGF-pathway inhibitors in patients with poor prognostic features. Poor-risk patients need to be considered as a heterogeneous population. Further understanding of biomarkers can lead to a better selection of patients who may benefit the most from treatment and improvements in prognosis. The presence of poor Karnofsky scores and liver or CNS disease may affect the outcome of these patients much more than other identified factors. This consideration may provide the rationale to further stratify poor-risk patients further subgroups destined to receive either cure or palliation.

Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery--a prospective cohort study.

PubMed

Haase-Fielitz, Anja; Bellomo, Rinaldo; Devarajan, Prasad; Story, David; Matalanis, George; Dragun, Duska; Haase, Michael

2009-02-01

To compare the value of novel with conventional serum biomarkers in the prediction of acute kidney injury (AKI) in adult cardiac surgical patients according to preoperative renal function. Single-center, prospective observational study. Tertiary hospital. One hundred adult cardiac surgical patients. We measured concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL), and serum cystatin C, and creatinine and urea at baseline, on arrival in the intensive care unit (ICU) and at 24 hours postoperatively. We assessed such biomarkers in relation to the development of AKI (>50% increase in creatinine from baseline) and to a composite end point (need for renal replacement therapy and in-hospital mortality). We defined an area under the receiver operating characteristic curve of 0.60-0.69 as poor, 0.70-0.79 as fair, 0.80-0.89 as good, and 0.90-1.00 as excellent in terms of predictive value. On arrival in ICU, plasma NGAL and serum cystatin C were of good predictive value, but creatinine and urea were of poor predictive value. After exclusion of patients with preoperative renal impairment (estimated glomerular filtration rate <60 mL/min), the predictive performance for AKI of all renal biomarkers on arrival in ICU remained unchanged except for cystatin C, which was of fair value in such patients. At 24 hours postoperatively, all renal biomarkers were of good predictive value. On arrival in ICU, novel biomarkers were superior to conventional biomarkers (p < 0.05). Plasma NGAL (p = 0.015) and serum cystatin C (p = 0.007) were independent predictors of AKI and of excellent value in the prediction of the composite end point. Early postoperative measurement of plasma NGAL was of good value in identifying patients who developed AKI after adult cardiac surgery. Plasma NGAL and serum cystatin C were superior to conventional biomarkers in the prediction of AKI and were also of prognostic value in this setting.

[Membranous nephropathy: Pathophysiology and natural history].

PubMed

Seitz-Polski, Barbara; Lambeau, Gérard; Esnault, Vincent

2017-04-01

Membranous nephropathy is a major cause of nephrotic syndrome in adults, with various etiologies and outcomes. One third of patients enter spontaneous remission with blockade of the renin-angiotensin system, one third develop a persistent nephrotic syndrome, while another third of patients develop end-stage kidney disease and 40% of them relapse after kidney transplantation. Treatment of membranous nephropathy remains controversial. Immunosuppressive therapy is only recommended in case of renal function deterioration or persistent nephrotic syndrome after 6months of renin-angiotensin system blockade. Therefore, delayed immunosuppressive treatments may lead to significant and potentially irreversible complications. For long, no biological markers could predict clinical outcome and guide therapy. The discovery of autoantibodies to the phospholipase A2 receptor (PLA2R1) in 2009, and to the thrombospondin type 1 domain containing 7A (THSD7A) in 2014 in respectively 70 and 5% of patients with membranous nephropathy were major breakthroughs. The passive infusion of human anti-THSD7A antibodies in mouse induces proteinuria and membranous nephropathy. The identification of these antigens has allowed developing diagnostic and prognostic tests. High anti-PLA2R1 titers at time of diagnosis predict a poor renal outcome. Anti-PLA2R1 antibodies can bind at least three different domains of PLA2R1. Epitope spreading with binding of two or three of these antigenic domains is associated with active membranous nephropathy and poor renal survival. These new tools could help us to monitor disease severity and to predict renal prognosis for a better selection of patients that should benefit of early immunosuppressive therapy. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Cardiovascular disease in live related renal transplantation.

PubMed

Kaul, A; Sharm, R K; Gupta, A; Sinha, N; Singh, U

2011-11-01

Cardiovascular disease has become the leading cause of morbidity and mortality in renal transplant recipients, although its pathogenesis and treatment are poorly understood. Modifiable cardiovascular risk factors and graft dysfunction both play an important role in development of post transplant cardiovascular events. Prevalence of cardiovascular disease was studied in stable kidney transplant patients on cyclosporine based triple immunosuppression in relation to the various risk factors and post transplant cardiovascular events. Analysis of 562 post transplant patients with stable graft function for 6 months, the patients were evaluated for cardiovascular events in post transplant period. Pre and post transplant risk factors were analyzed using the COX proportional hazard model. 174 patients had undergone pre transplant coronary angiography, 15 of these patients underwent coronary revascularization (angioplasty in 12, CABG in 3). The prevalence of CAD was 7.2% in transplant recipients. Of 42 patients with CAD 31 (73.8%) had cardiovascular event in post transplant period. Age > or = 40 yrs, male sex, graft dysfunction, diabetes as primary renal disease, pre transplant cardiovascular event, chronic rejection showed significant correlation in univariate analysis and there was significant between age > or = 40 years (OR = 2.16 with 95% CI, 0.977-4.78) S creatinine > or = 1.4 mg % (OR = 2.40 with 95% CI, 1.20 - 4.82), diabetes as primary disease (OR with 95% CI 3.67, 3.2-14.82), PTDM (OR 3.67, 95% CI 1.45-9.40), pre-transplant cardiovascular disease (OR 4.14, 95% CI .38-13.15) with post transplant cardiovascular event on multivariate analysis. There was poor patient and graft survival among those who suffered post transplant cardiovascular event. The incidence of cardiovascular disease continues to be high after renal transplantation and modifiable risk factors should be identified to prevent occurrence of events in post transplant period.

Assessment of the relationship between renal volume and renal function after minimally-invasive partial nephrectomy: the role of computed tomography and nuclear renal scan.

PubMed

Bertolo, Riccardo; Fiori, Cristian; Piramide, Federico; Amparore, Daniele; Barrera, Monica; Sardo, Diego; Veltri, Andrea; Porpiglia, Francesco

2018-05-14

To evaluate the correlation between the loss of renal function as assessed by Tc99MAG-3 renal scan and the loss of renal volume as calculated by volumetric assessment on CT-scan in patients who underwent minimally-invasive partial nephrectomy (PN). PN prospectively-maintained database was retrospectively queried for patients who underwent minimally-invasive PN (2012-2017) for renal mass

Comparative Evaluation of Periodontal Status of Chronic Renal Failure Patients and Systemically Healthy Individuals.

PubMed

Gupta, Radhika; Kumar, Uttam; Mallapragada, Siddharth; Agarwal, Pallavi

2018-03-01

Periodontitis, a chronic infectious disease, affects most of the population at one time or the other and its expression is a combination of hosts, microbial agents, and environmental factors. Extensive literature exists for the relationship between periodontal disease and diabetes mellitus, cardiovascular diseases, and adverse pregnancy outcomes. Only a few studies performed in a limited number of patients have reported peri-odontal health status in chronic renal failure patients. Hence, the aim of the present study is to assess and compare the periodontal status of patients with chronic renal failure undergoing dialysis, predialysis with systemically healthy individuals. A total of 90 patients were divided into three groups. Group I: 30 renal dialysis patients. Group II: 30 predialysis patients. Control group comprised 30 systemically healthy patients who formed group III. Periodontal examination was carried out using oral hygiene index-simplified (OHI-S), plaque index (PI), gingival index (GI), probing depth, and clinical attachment loss. The results of the study showed that the periodontal status of patients with chronic renal failure undergoing dialysis (dialysis group) and patients with chronic renal failure not undergoing renal dialysis (predialysis) when compared with systemically healthy subjects showed significantly higher mean scores of OHI-S, PI, and clinical attachment loss. Thus, patients with chronic renal failure showed poor oral hygiene and higher prevalence of periodontal disease. The dental community's awareness of implications of poor health within chronic renal failure patients should be elevated.

Zinc restriction during different periods of life: influence in renal and cardiovascular diseases.

PubMed

Tomat, Analía Lorena; Costa, María de los Ángeles; Arranz, Cristina Teresa

2011-04-01

Micronutrient undernutrition during critical periods of growth has become an important health issue in developing and developed countries, particularly among pregnant women and children having an imbalanced diet. Zinc is a widely studied microelement in infant feeding because it is a component of several enzymes involved in intermediary metabolism ranging from growth to cell differentiation and metabolism of proteins, carbohydrates, and lipids. Human and experimental studies have reported an association between zinc deficiency and the etiopathogenesis of cardiovascular and renal diseases like hypertension, atherosclerosis, congestive heart failure, coronary heart disease, and diabetes. The main links between the development of these pathologies and zinc deficiency are multiple mechanisms involving oxidative stress damage, apoptosis, and inflammation. A substantial body of evidence suggests that a poor in utero environment elicited by maternal dietary or placental insufficiency may "programme" susceptibility in the fetus to later development of cardiovascular, renal, metabolic, and endocrine diseases. Zinc deficiency in rats during intrauterine and postnatal growth can also be considered a model of fetal programming of cardiovascular and renal diseases in adult life. Dietary zinc restriction during fetal life, lactation, and/or postweaning induces an increase in arterial blood pressure and impairs renal function in adult life. This review focuses on the contributions of experimental and clinical studies to current knowledge of the physiologic role of zinc in the cardiovascular and renal systems. Moreover, this review examines the relationship between zinc deficiency during different periods of life and the development of cardiovascular and renal diseases in adult life. Copyright © 2011 Elsevier Inc. All rights reserved.

Long Noncoding RNA Small Nucleolar RNA Host Gene 1 (SNHG1) Promotes Renal Cell Carcinoma Progression and Metastasis by Negatively Regulating miR-137.

PubMed

Zhao, Shiyue; Wang, Yangwei; Luo, Manyu; Cui, Wenpeng; Zhou, Xiaoxi; Miao, Lining

2018-06-06

BACKGROUND Data on the expression of RCC tissues from the GEO database and patient survival data from TCGA were used to explore the prognostic significance of long noncoding RNA SNHG1. SNHG1 has been reported to participate in the development of several cancers, but, the underlying mechanism of SNHG1 in renal cell carcinoma (RCC) has not been reported. The purpose of our study was to investigate the potential function of SNHG1 in RCC. MATERIAL AND METHODS The expression of SNHG1 in 40 cases of RCC and adjacent normal tissues and 5 cell lines was detected by qRT-PCR. Cell proliferation, Transwell assay, and Western blotting assay were carried out to investigate the biological function of SNHG1. A rescue experiment was performed to verify that miR-137 can partly impede the effect of SNHG1 on renal cancer cells. RESULTS SNHG1 was identified to be overexpressed in RCC tissues and RCC cell lines. High levels of SNHG1 were correlated with poor prognosis of RCC patients. Knockdown of SNHG1 suppressed the proliferation, invasion, and EMT capacity in RCC. Moreover, miR-137 abrogated the effect of SNHG1 on RCC. CONCLUSIONS SNHG1 is significantly upregulated in RCC and renal cancer cell lines. Overexpression of SNHG1 participates in RCC tumorigenesis by regulating miR-137.

Long Noncoding RNA Small Nucleolar RNA Host Gene 1 (SNHG1) Promotes Renal Cell Carcinoma Progression and Metastasis by Negatively Regulating miR-137

PubMed Central

Zhao, Shiyue; Wang, Yangwei; Luo, Manyu; Cui, Wenpeng; Zhou, Xiaoxi

2018-01-01

Background Data on the expression of RCC tissues from the GEO database and patient survival data from TCGA were used to explore the prognostic significance of long noncoding RNA SNHG1. SNHG1 has been reported to participate in the development of several cancers, but, the underlying mechanism of SNHG1 in renal cell carcinoma (RCC) has not been reported. The purpose of our study was to investigate the potential function of SNHG1 in RCC. Material/Methods The expression of SNHG1 in 40 cases of RCC and adjacent normal tissues and 5 cell lines was detected by qRT-PCR. Cell proliferation, Transwell assay, and Western blotting assay were carried out to investigate the biological function of SNHG1. A rescue experiment was performed to verify that miR-137 can partly impede the effect of SNHG1 on renal cancer cells. Results SNHG1 was identified to be overexpressed in RCC tissues and RCC cell lines. High levels of SNHG1 were correlated with poor prognosis of RCC patients. Knockdown of SNHG1 suppressed the proliferation, invasion, and EMT capacity in RCC. Moreover, miR-137 abrogated the effect of SNHG1 on RCC. Conclusions SNHG1 is significantly upregulated in RCC and renal cancer cell lines. Overexpression of SNHG1 participates in RCC tumorigenesis by regulating miR-137. PMID:29874202

The paradox of transient worsening renal function in patients with acute heart failure: the role of B-type natriuretic peptide and diuretic response.

PubMed

Ruocco, Gaetano; Nuti, Ranuccio; Giambelluca, Amalia; Evangelista, Isabella; De Vivo, Oreste; Daniello, Cosimo; Palazzuoli, Alberto

2017-11-01

Worsening renal function (WRF) occurs in one-third of patients hospitalized for acute decompensated heart failure. Recently, WRF was categorized in two subtypes: persistent and transient WRF. Thus, we sought to investigate the different prognostic impact of persistent vs. transient WRF; we also evaluate the relation of two WRF phenotypes with congestion, B-type natriuretic peptide (BNP) changes, and diuretic response at discharge. The prospective was a single centre study including patients screened for interventional Diur-heart failure Trial (NCT01441245). Patients were eligible if they were admitted with a primary diagnosis of acute heart failure with evidence of volume overload. Persistent WRF was defined as a sustained creatinine increase by at least 0.3 mg/dl throughout the hospitalisation; transient WRF was defined as creatinine increase by at least 0.3 mg/dl within 72 h and a return to baseline levels at discharge. Patients were followed for 6 months after discharge. Our population included 192 acute decompensated heart failure patients. In total, 61 patients developed persistent WRF and 29 developed transient WRF. Patients with persistent WRF showed a lower mean urine output with respect to the transient WRF group and patients with preserved renal function (1618 ± 374 vs. 2132 ± 392 vs. 2075 ± 442 ml; P < 0.001). Similarly, patients with transient WRF demonstrated a higher rate of BNP decrease more than 30% than seen in patients with stable creatinine levels and in the persistent WRF group (95 vs. 76 vs. 54%; P = 0.001). Univariate Cox regression analysis demonstrated that BNP decrease less than 30% [HR 2.15 (1.40-3.40); P < 0.001] and persistent WRF [HR 1.70 (1.11-2.61); P = 0.01] were related to poor outcome; conversely, transient WRF should be considered as a protective factor [HR 0.42 (0.19-0.93); P = 0.03]. In the multivariable model, only persistent WRF appeared to be related to poor prognosis [HR 1.61 (1.02-2.57); P = 0.04]. WRF occurring during hospitalization has a different significance: transient deterioration appears to be associated with a favourable clinical course; conversely, persistent WRF is related to poor outcome.

Blocking rpS6 Phosphorylation Exacerbates Tsc1 Deletion–Induced Kidney Growth

PubMed Central

Wu, Huijuan; Chen, Jianchun; Xu, Jinxian; Dong, Zheng; Meyuhas, Oded

2016-01-01

The molecular mechanisms underlying renal growth and renal growth–induced nephron damage remain poorly understood. Here, we report that in murine models, deletion of the tuberous sclerosis complex protein 1 (Tsc1) in renal proximal tubules induced strikingly enlarged kidneys, with minimal cystogenesis and occasional microscopic tumorigenesis. Signaling studies revealed hyperphosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and increased phosphorylation of ribosomal protein S6 (rpS6) in activated renal tubules. Notably, knockin of a nonphosphorylatable rpS6 in these Tsc1-mutant mice exacerbated cystogenesis and caused drastic nephron damage and renal fibrosis, leading to kidney failure and a premature death rate of 67% by 9 weeks of age. In contrast, Tsc1 single-mutant mice were all alive and had far fewer renal cysts at this age. Mechanistic studies revealed persistent activation of mammalian target of rapamycin complex 1 (mTORC1) signaling causing hyperphosphorylation and consequent accumulation of 4E-BP1, along with greater cell proliferation, in the renal tubules of Tsc1 and rpS6 double-mutant mice. Furthermore, pharmacologic treatment of Tsc1 single-mutant mice with rapamycin reduced hyperphosphorylation and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6. Rapamycin also exacerbated cystic and fibrotic lesions and impaired kidney function in these mice, consequently leading to a premature death rate of 40% within 2 weeks of treatment, despite destroying tumors and decreasing kidney size. These findings indicate that Tsc1 prevents aberrant renal growth and tumorigenesis by inhibiting mTORC1 signaling, whereas phosphorylated rpS6 suppresses cystogenesis and fibrosis in Tsc1-deleted kidneys. PMID:26296742

Presence of transient hydronephrosis immediately after surgery has a limited influence on renal function 1 year after ileal neobladder construction.

PubMed

Narita, Takuma; Hatakeyama, Shingo; Koie, Takuya; Hosogoe, Shogo; Matsumoto, Teppei; Soma, Osamu; Yamamoto, Hayato; Yoneyama, Tohru; Tobisawa, Yuki; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara

2017-08-31

Urinary tract obstruction and postoperative hydronephrosis are risk factor for renal function deterioration after orthotopic ileal neobladder construction. However, reports of relationship between transient hydronephrosis and renal function are limited. We assess the influence of postoperative transient hydronephrosis on renal function in patients with orthotopic ileal neobladder construction. Between January 2006 and June 2013, we performed radical cystectomy in 164 patients, and 101 received orthotopic ileal neobladder construction. This study included data available from 64 patients with 128 renal units who were enrolled retrospectively. The hydronephrosis grade of each renal unit scored 0-4. The patients were divided into 4 groups according to the grade of hydronephrosis: control, low, intermediate, and high. The grade of postoperative hydronephrosis was compared with renal function 1 month and 1 year after surgery. There were no significant differences in renal function before surgery between groups. One month after surgery, the presence of hydronephrosis was significantly associated with decreased renal function. However, 1 year after urinary diversion hydronephrosis grades were improved significantly, and renal function was comparable between groups. Postoperative hydronephrosis at 1 month had no significant influence on renal function 1 year after ileal neobladder construction. Limitations include retrospective design, short follow-up periods, and a sample composition. The presence of transient hydronephrosis immediately after surgery may have limited influence on renal function 1 year after ileal neobladder construction.

Cystatin C as an early marker of acute kidney injury in septic shock.

PubMed

Ortuño-Andériz, F; Cabello-Clotet, N; Vidart-Simón, N; Postigo-Hernández, C; Domingo-Marín, S; Sánchez-García, M

2015-03-01

To describe the utility of determining plasma cystatinC concentrations in the diagnosis of acute incident kidney injury in septic shock. Prospective series of 50 patients with septic shock and plasma creatinine levels <2mg/dL hospitalized in an intensive care unit. Clinical and laboratory follow-ups were conducted, with measurements of cystatinC, urea and plasma creatinine levels from the diagnosis of septic shock to 5days later. The severity of the septic shock was assessed with the RIFLE scale. Twenty patients (40%) developed acute kidney injury: 8 (16%) were categorized as RIFLE-R, 5 (10%) as RIFLE-I and 7 (14%) as RIFLE-F. All patients categorized as RIFLE-F required extracorporeal renal clearance. Eighteen (36%) patients died, 8 (20%) of whom had developed acute kidney injury in their evolution. There was poor correlation between plasma creatinine and cystatin C levels (r=.501; P=.001), which disappeared upon reaching any degree of renal impairment on the RIFLE scale. CystatinC levels increased earlier and were better able to identify patients who would develop serious renal function impairment (RIFLE-F) than creatinine and urea levels. The initial cystatinC levels were related to mortality at 30days (OR=1.16; 95%CI: 03-.85). For patients who developed acute septic kidney injury, the plasma cystatinC levels increased before the classical markers of renal function. CystatinC also constitutes a severity biomarker that correlates with progression to RIFLE-F, the need for extrarenal clearance and, ultimately, mortality. This precocity could be useful for starting measures that prevent the progression of renal dysfunction. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

PubMed

Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-14

Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

Renal Perfusion and Function during Pneumoperitoneum: A Systematic Review and Meta-Analysis of Animal Studies

PubMed Central

Warlé, Michiel C.; Hooijmans, Carlijn R.

2016-01-01

Both preclinical and clinical studies indicate that raised intra-abdominal pressure (IAP) associated with pneumoperitoneum during laparoscopic surgical procedures can cause renal damage, the severity of which may be influenced by variables such as pressure level and duration. Several of these variables have been investigated in animal studies, but synthesis of all preclinical data has not been performed. This systematic review summarizes all available pre-clinical evidence on this topic, including an assessment of its quality and risk of bias. We performed meta-analysis to assess which aspects of the pneumoperitoneum determine the severity of its adverse effects. A systematic search in two databases identified 55 studies on the effect of pneumoperitoneum on renal function which met our inclusion criteria. There was high heterogeneity between the studies regarding study design, species, sex, pressure and duration of pneumoperitoneum, and type of gas used. Measures to reduce bias were poorly reported, leading to an unclear risk of bias in the majority of studies. Details on randomisation, blinding and a sample size calculation were not reported in ≥80% of the studies. Meta-analysis showed an overall increase in serum creatinine during pneumoperitoneum, and a decrease in urine output and renal blood flow. Subgroup analysis indicated that for serum creatinine, this effect differed between species. Subgroup analysis of pressure level indicated that urine output decreased as IAP level increased. No differences between types of gas were observed. Data were insufficient to reliably assess whether sex or IAP duration modulate the effect of pneumoperitoneum. Four studies assessing long-term effects indicated that serum creatinine normalized ≥24 hours after desufflation of pneumoperitoneum at 15mmHg. We conclude that harmful effects on renal function and perfusion during pneumoperitoneum appear to be robust, but evidence on long-term effects is very limited. The reliability and clinical relevance of these findings for healthy patients and patients at high risk of renal impairment remain uncertain. We emphasize the need for rigorous reporting of preclinical research methodology, which is of vital importance for clinical translation of preclinical data. PMID:27657740

Hyporeninemic hypoaldosteronism in a patient with diabetes mellitus: an unforgettable case report.

PubMed

Chelaghma, Naziha; Oyibo, Samson O

2018-01-01

A 58-year-old man presented with a 3-year history of chronic and intermittent hyperkalemia requiring recurrent attendances to the emergency department for urgent treatment. His medical history included secondary diabetes mellitus following a bout of acute pancreatitis and a previous splenectomy for a spontaneous splenic rupture. He also had a history of prolonged use of non-steroidal anti-inflammatory drugs for back pain and painful neuropathy. He was not on any medication or diet that would cause a raised serum potassium level and his renal function was normal. He was on a basal-bolus insulin regimen but his diabetes control had been poor for several years. As the hyperkalemia had gone on for so long in the presence of normal renal function, he went on to have further tests. Adrenal insufficiency had been ruled out following a short Synacthen test. Further investigations revealed low serum aldosterone levels and inappropriately low serum renin levels in the presence of hyperkalemia. This was suggestive of hyporeninemic hypoaldosteronism (HH). He was then treated with fludrocortisone and furosemide and his serum potassium levels remained normal. Additionally, he did not require any more emergency admissions to treat hyperkalemia thereafter. It was concluded that the HH-induced hyperkalemia was caused by diabetes mellitus or due to a combination of diabetes and prolonged use of non-steroidal anti-inflammatory drugs. The absence of renal impairment may have contributed to the delay in diagnosis. HH is a commonly overlooked cause of hyperkalemia. This case highlights the fact that it should always be suspected when unexplained hyperkalemia is found in patients with only mild-moderately impaired renal function, especially in the presence of diabetes mellitus.

Renal rickets-practical approach

PubMed Central

Sahay, Manisha; Sahay, Rakesh

2013-01-01

Rickets/osteomalacia is an important problem in a tropical country. Many cases are due to poor vitamin D intake or calcium deficient diets and can be corrected by administration of calcium and vitamin D. However, some cases are refractory to vitamin D therapy and are related to renal defects. These include rickets of renal tubular acidosis (RTA), hypophosphatemic rickets, and vitamin D dependent rickets (VDDR). The latter is due to impaired action of 1α-hydroxylase in renal tubule. These varieties need proper diagnosis and specific treatment. PMID:24251212

Impact of pretransplant renal function on survival after liver transplantation.

PubMed

Gonwa, T A; Klintmalm, G B; Levy, M; Jennings, L S; Goldstein, R M; Husberg, B S

1995-02-15

To determine the effect of pretransplant liver function on survival following orthotopic liver transplantation and to quantify the effects of cyclosporine administration on long-term renal function in patients undergoing liver transplant, we performed an analysis of a prospectively maintained database. Data from 569 consecutive patients undergoing liver transplantation alone who were treated with CsA for immunosuppression were used for this study. Actuarial graft and patient survival rates were calculated using Kaplan-Meier statistics. Glomerular filtration rates, serum creatinine, and the use of various immunosuppressives were analyzed for this study. The initial analysis demonstrated that patients presenting for liver transplant with hepatorenal syndrome have a significantly decreased acturial patient survival after liver transplant at 5 years compared with patients without hepatorenal syndrome (60% vs. 68%, P < 0.03). Patients with hepatorenal syndrome recovered their renal function after liver transplant. Patients who had hepatorenal syndrome were sicker and required longer stays in the intensive care unit, longer hospitalizations, and more dialysis treatments after transplantation compared with patients who did not have hepatorenal syndrome. The incidence of end-stage renal disease after liver transplantation in patients who had hepatorenal syndrome was 7%, compared with 2% in patients who did not have hepatorenal syndrome. To more fully examine the effect of pretransplant renal function on posttransplant survival, the non-hepatorenal syndrome patients were divided into quartiles depending upon their pretransplant renal function. The patients with the lowest pretransplant renal function had the same survival as the patients with the highest pretransplant renal function. In addition, there was no increased incidence of acute or chronic rejection in any of the groups. The patients with the lower pretransplant renal function were treated with more azathioprine to maintain renal function and had a negligible decrease in glomerular filtration rate following transplant. Conversely, patients with the highest level of renal function pretransplant had a 40% decline in renal function in the first year, but maintained stable renal function up to 4 years after transplant. We conclude that pretransplant renal function other than hepato-renal syndrome has no effect on patient survival after orthotopic liver transplant. Renal function after liver transplant is stable after an initial decline, despite continued administration of CsA.(ABSTRACT TRUNCATED AT 400 WORDS)

Are gatekeepers to renal services referring patients equitably?

PubMed

Kee, Frank; Reaney, Elizabeth; Savage, Gerard; O'Reilly, Dermot; Patterson, Chris; Maxwell, Peter; Fogarty, Damian

2007-01-01

Patients with chronic kidney disease (CKD) benefit from specialist interventions to retard progression of renal failure and prevent cardiovascular events. Certain patient groups have poor access to specialist renal services when dialysis is required. This study used a population-based laboratory database to investigate access to and timeliness of referral to renal specialists relatively early in the course of the disease. All tests for serum creatinine and haemoglobin (Hb) A(1)c in Northern Ireland in a two-year period (2001 and 2002) were retrieved for 345,441 adults. Of these, 16,856 patients had at least one serum creatinine level above 150 micromol/L in 2001 not deemed to be due to acute renal failure (crude prevalence 1.42%). This cohort was followed until the end of 2002 and the differences in the time to referral to a specialist were assessed using Cox's proportional hazards regression. Diabetic patients, older patients and those living in deprived areas were significantly more likely to have serum creatinine testing, compared with non-diabetic, younger and those living in more affluent areas. Delays in referral to renal specialists for patients with raised serum creatinine levels were significantly shorter among diabetic patients, women, younger individuals, those living in rural areas, those living close to renal centres and those living in deprived areas. Overall, only 19% of diabetic patients and 6% of non-diabetic patients who had CKD had seen a renal specialist within 12 months of their index creatinine test. Contrary to other diseases, disadvantaged patients do not seem to be under-investigated for renal disease compared with their more affluent neighbours and are generally referred earlier for specialist assessment. However, the absolute rate of timely specialist assessment is low. Recent changes in referral criteria for CKD will result in more referrals and will have serious resource implications. Opportunities for health gain among patients with declining renal function are being missed, particularly among the old and those living furthest from specialist centres.

Clinical course of dengue fever and its impact on renal function in renal transplant recipients and patients with chronic kidney disease.

PubMed

Arun Thomas, E T; George, Jacob; Sruthi, Devi; Vineetha, N S; Gracious, Noble

2018-04-01

Dengue fever is a mosquito-borne viral disease endemic in many tropical and sub-tropical countries. There is only limited data in the literature about dengue fever in renal transplant recipients and patients with chronic kidney disease. This study compares the clinical course of dengue fever and its impact on renal function in renal transplant recipients, patients with chronic kidney disease and patients with normal base line renal function. An observational study was conducted from 1 st May to 31 st July 2017, at a tertiary care centre of South India. A major epidemic of dengue had occurred during the study period. Twelve renal transplant recipients, 22 patients with CKD and 58 patients with normal baseline renal function (control group) admitted with dengue fever were prospectively studied. Nadir WBC count was lowest in renal transplant recipients (2575 + 1187/mm 3 ), [P<0.001]. Renal transplant recipients took more time for normalisation of platelet count (6 + 4.5 days), [P<0.001]. All 22 patients with CKD and 11 of 12 renal transplant recipients had worsening of renal function where as only 17 of 58 patients in the control group had worsening [P<0.001]. Sixteen patients with CKD, one renal transplant recipient and none among control group required hemodialysis [P<0.001]. Dialysis requiring patients had more hemoconcentration (52.5+ 19.9% increase in haemoglobin), [P<0.001]. Seven patients with CKD were dialysis dependent at the end of 2 weeks. Clinical features of dengue fever were different in renal transplant recipients and patients with CKD. Severe worsening of renal function was common in CKD patients. Worsening of renal function in renal transplant recipients was less severe and transient. This article is protected by copyright. All rights reserved.

Dioctophyma renale (Goeze, 1782) Infection in a Domestic Dog from Hamedan, Western Iran

PubMed Central

ZOLHAVARIEH, Seyed Masoud; NORIAN, Alireza; YAVARI, Morteza

2016-01-01

Dioctophyma renale infection is found in a wide range of mammalian species, typically in temperate areas of the world. Here, we report for the first time, the parasitism of a domestic dog by D. renale in Hamedan, Iran, a mountainous cold region, lacking significant amounts of rainfall, high humidity and temperature. A 2.5 yr old male mixed breed dog was presented with a two months history of progressive hematuria and muscle weakness. Complete blood count and serum biochemistry were performed with results indicating impaired renal function. Urinalysis, showed hematuria as well as parasitic eggs, suggestive of D. renale infection. Urinary system ultrasonography revealed a hypoecogenic tubular structure in the right kidney. The animal was treated with fenbendazole (45 mg/kg, PO, QD - five days) and ivermectin (0.02 mg/kg, SC, single dose). One week later, repeated laboratory examination confirmed presence of at least one alive worm in the affected kidney. A unilateral nephrectomy was performed; one female (60 × 5 cm) and one male (30 × 3.8 cm) live worm were taken out of the extremely thin walled right kidney. One month later, due to failure of the remained kidney and poor condition, the patient deceased. We conclude that dioctophymosis can be found in cold and or relatively dry area. Moreover, the results showed that the worm was not affected with common anthelmintic drugs. PMID:27095981

Dioctophyma renale (Goeze, 1782) Infection in a Domestic Dog from Hamedan, Western Iran.

PubMed

Zolhavarieh, Seyed Masoud; Norian, Alireza; Yavari, Morteza

2016-01-01

Dioctophyma renale infection is found in a wide range of mammalian species, typically in temperate areas of the world. Here, we report for the first time, the parasitism of a domestic dog by D. renale in Hamedan, Iran, a mountainous cold region, lacking significant amounts of rainfall, high humidity and temperature. A 2.5 yr old male mixed breed dog was presented with a two months history of progressive hematuria and muscle weakness. Complete blood count and serum biochemistry were performed with results indicating impaired renal function. Urinalysis, showed hematuria as well as parasitic eggs, suggestive of D. renale infection. Urinary system ultrasonography revealed a hypoecogenic tubular structure in the right kidney. The animal was treated with fenbendazole (45 mg/kg, PO, QD - five days) and ivermectin (0.02 mg/kg, SC, single dose). One week later, repeated laboratory examination confirmed presence of at least one alive worm in the affected kidney. A unilateral nephrectomy was performed; one female (60 × 5 cm) and one male (30 × 3.8 cm) live worm were taken out of the extremely thin walled right kidney. One month later, due to failure of the remained kidney and poor condition, the patient deceased. We conclude that dioctophymosis can be found in cold and or relatively dry area. Moreover, the results showed that the worm was not affected with common anthelmintic drugs.

Heart failure and kidney dysfunction: epidemiology, mechanisms and management.

PubMed

Schefold, Joerg C; Filippatos, Gerasimos; Hasenfuss, Gerd; Anker, Stefan D; von Haehling, Stephan

2016-10-01

Heart failure (HF) is a major health-care problem and the prognosis of affected patients is poor. HF often coexists with a number of comorbidities of which declining renal function is of particular importance. A loss of glomerular filtration rate, as in acute kidney injury (AKI) or chronic kidney disease (CKD), independently predicts mortality and accelerates the overall progression of cardiovascular disease and HF. Importantly, cardiac and renal diseases interact in a complex bidirectional and interdependent manner in both acute and chronic settings. From a pathophysiological perspective, cardiac and renal diseases share a number of common pathways, including inflammatory and direct, cellular immune-mediated mechanisms; stress-mediated and (neuro)hormonal responses; metabolic and nutritional changes including bone and mineral disorder, altered haemodynamic and acid-base or fluid status; and the development of anaemia. In an effort to better understand the important crosstalk between the two organs, classifications such as the cardio-renal syndromes were developed. This classification might lead to a more precise understanding of the complex interdependent pathophysiology of cardiac and renal diseases. In light of exceptionally high mortality associated with coexisting HF and kidney disease, this Review describes important crosstalk between the heart and kidney, with a focus on HF and kidney disease in the acute and chronic settings. Underlying molecular and cellular pathomechanisms in HF, AKI and CKD are discussed in addition to current and future therapeutic approaches.

Geometric Alteration of Renal Arteries After Fenestrated Grafting and the Impact on Renal Function.

PubMed

Ou, Jiale; Chan, Yiu-Che; Chan, Crystal Yin-Tung; Cheng, Stephen W K

2017-05-01

This study aims to investigate the degree of geometric change on renal arteries and its impact on renal function after fenestrated endovascular aortic repair (fEVAR). Twenty-five patients with fEVAR were included. There were 47 renal arteries target vessels, and 43 of these (22 left and 21 right vessels) stented successfully. Their preoperative and first postoperative follow-up computed tomography (CT) images were reconstructed using the Aquarius workstation (TeraRecon, San Mateo, CA, USA). The superior mesenteric artery (SMA) or celiac axis (if SMA was stented) was appointed as reference origin. The longitudinal orientation of a renal artery or a stent was represented by a takeoff angle (ToA) between the renal artery or stent and the distal abdominal aorta. The postoperative stent ToAs were compared with those of preoperative renal arteries. Preoperative and short-term postoperative serum creatinine levels were measured. Renal function impairment was indicated as a >30% or >2.0 mg/dL rise in serum creatinine compared to the preoperative level. The relationship between postoperative renal function impairment and the stent orientation or geometric changes in renal arteries was correlated. The patency rate of renal arteries was 100% at the first postoperative CT review. The average ToAs of both renal arteries were significantly enlarged after stenting (P < 0.05). Seven stent deformations (16.3%) in four patients (16.0%) were observed. They were attributed to caudal misalignment of the fenestrated stent graft (n = 6) or inaccurate graft sizing (n = 1). There was no stent fracture or target vessel loss. Postoperatively, nine patients (36.0%) at day 1 and 10 patients (41.7%) after 3 months suffered the renal function impairment. This was found not to be associated with the stent angulation or angular change of the renal arteries (both P > 0.05). The three patients with stent deformation due to misalignment suffered postoperative renal function impairment and continuing deterioration in renal function. Implanted renal stents could angulate renal arteries more cephalad after fenestrated stenting. Postoperative renal function impairment was not associated with the stent orientation and changes in vessel orientation. Accurate fenestrated alignment is important to maintain stent performance and preserve renal function. Copyright © 2017 Elsevier Inc. All rights reserved.

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

PubMed Central

Tullos, Nathan; Stewart, Nicholas J.; Surles, Bret

2015-01-01

Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD. PMID:25377076

Predictive abilities of cardiovascular biomarkers to rapid decline of renal function in Chinese community-dwelling population: a 5-year prospective analysis.

PubMed

Fu, Shihui; Liu, Chunling; Luo, Leiming; Ye, Ping

2017-11-09

Predictive abilities of cardiovascular biomarkers to renal function decline are more significant in Chinese community-dwelling population without glomerular filtration rate (GFR) below 60 ml/min/1.73m 2 , and long-term prospective study is an optimal choice to explore this problem. Aim of this analysis was to observe this problem during the follow-up of 5 years. In a large medical check-up program in Beijing, there were 948 participants with renal function evaluated at baseline and follow-up of 5 years. Physical examinations were performed by well-trained physicians. Blood samples were analyzed by qualified technicians in central laboratory. Median rate of renal function decline was 1.46 (0.42-2.91) mL/min/1.73m 2 /year. Rapid decline of renal function had a prevalence of 23.5% (223 participants). Multivariate linear and Logistic regression analyses confirmed that age, sex, baseline GFR, homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP) had independently predictive abilities to renal function decline rate and rapid decline of renal function (p < 0.05 for all). High-sensitivity cardiac troponin T (hs-cTnT), carotid femoral pulse wave velocity and central augmentation index had no statistically independent association with renal function decline rate and rapid decline of renal function (p > 0.05 for all). Homocysteine and NT-proBNP rather than hs-cTnT had independently predictive abilities to rapid decline of renal function in Chinese community-dwelling population without GFR below 60 ml/min/1.73m 2 . Baseline GFR was an independent factor predicting the rapid decline of renal function. Arterial stiffness and compliance had no independent effect on rapid decline of renal function. This analysis has a significant implication for public health, and changing the homocysteine and NT-proBNP levels might slow the rapid decline of renal function.

The additive effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 function in diabetic rats.

PubMed

Thongnak, Laongdao; Pongchaidecha, Anchalee; Jaikumkao, Krit; Chatsudthipong, Varanuj; Chattipakorn, Nipon; Lungkaphin, Anusorn

2017-10-19

Hyperglycemia-induced oxidative stress is usually found in diabetic condition. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, statins, are widely used as cholesterol-lowering medication with several "pleiotropic" effects in diabetic patients. This study aims to evaluate whether the protective effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 (Oat3) function involve the modulation of oxidative stress and pancreatic function in type 1 diabetic rats. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg BW). Atorvastatin and insulin as single or combined treatment were given for 4 weeks after diabetic condition had been confirmed. Diabetic rats demonstrated renal function and renal Oat3 function impairment with an increased MDA level and decreased SOD protein expression concomitant with stimulation of renal Nrf2 and HO-1 protein expression. Insulin plus atorvastatin (combined) treatment effectively restored renal function as well as renal Oat3 function which correlated with the decrease in hyperglycemia and oxidative stress. Moreover, pancreatic inflammation and apoptosis in diabetic rats were ameliorated by the combined drugs treatment. Therefore, atorvastatin plus insulin seems to exert the additive effect in improving renal functionby alleviating hyperglycemiaand the modulation of oxidative stress, inflammation and apoptosis.

Effects of continuous and pulsatile flows generated by ventricular assist devices on renal function and pathology.

PubMed

Miyamoto, Takuma; Karimov, Jamshid H; Fukamachi, Kiyotaka

2018-03-01

Continuous-flow (CF) left ventricular assist devices (LVADs) are widely used to treat end-stage heart failure. Despite substantial improvement in clinical results, numerous complications remain associated with this technology. Worsening renal function is one, associated with morbidity and mortality in patients supported by CF LVADs. The effects of CF LVAD support on renal function have been investigated since the mid-1990s by many research groups. Area covered: We review the current status of LVAD therapy, experimental results regarding the effects of types of flow generated by LVADs on renal function and pathology, changes in renal function after LVAD implant, the influence of renal function on outcomes, and risk factors for renal dysfunction post implant. This information was obtained through online databases and direct extraction of single studies. Expert commentary: Immediately after CF LVAD implantation, renal function improves temporarily as patients recover from the kidneys' previously low perfusion and congestive state. However, many studies have shown that this initially recovered renal function gradually declines during long-term CF LVAD support. Although it is known that CF LVAD support adversely affects renal function over the long term, just how it does has not yet been clearly defined in terms of clinical symptoms or signs.

Echocardiographic predictors of change in renal function with intravenous diuresis for decompensated heart failure.

PubMed

Gannon, Stephen A; Mukamal, Kenneth J; Chang, James D

2018-06-14

The aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion. A retrospective review of 363 patients admitted to a single centre for decompensated heart failure who underwent intravenous diuresis and transthoracic echocardiography was conducted. Clinical, echocardiographic, and renal function data were retrospectively collected. A multinomial logistic regression model was created to determine relative risk ratios for improved renal function (IRF) or worsening renal function (WRF). Within this cohort, 36% of patients experienced WRF, 35% had stable renal function, and 29% had IRF. Patients with WRF were more likely to have a preserved left ventricular ejection fraction compared with those with stable renal function or IRF (P = 0.02). Patients with IRF were more likely to have a dilated, hypokinetic right ventricle compared with those with stable renal function or WRF (P ≤ 0.01), although this was not significant after adjustment for baseline characteristics. Left atrial size, left ventricular linear dimensions, and diastolic function did not significantly predict change in renal function. An acute change in renal function occurred in 65% of patients admitted with decompensated heart failure. WRF was statistically more likely in patients with a preserved left ventricular ejection fraction. A trend towards IRF was noted in patients with global right ventricular dysfunction. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

When Partial Nephrectomy is Unsuccessful: Understanding the Reasons for Conversion from Robotic Partial to Radical Nephrectomy at a Tertiary Referral Center.

PubMed

Kara, Önder; Maurice, Matthew J; Mouracade, Pascal; Malkoç, Ercan; Dagenais, Julien; Nelson, Ryan J; Chavali, Jaya Sai S; Stein, Robert J; Fergany, Amr; Kaouk, Jihad H

2017-07-01

We sought to identify the preoperative factors associated with conversion from robotic partial nephrectomy to radical nephrectomy. We report the incidence of this event. Using our institutional review board approved database, we abstracted data on 1,023 robotic partial nephrectomies performed at our center between 2010 and 2015. Standard and converted cases were compared in terms of patients and tumor characteristics, and perioperative, functional and oncologic outcomes. Logistic regression analysis was done to identify predictors of radical conversion. The overall conversion rate was 3.1% (32 of 1,023 cases). The most common reasons for conversion were tumor involvement of hilar structures (8 cases or 25%), failure to achieve negative margins on frozen section (7 or 21.8%), suspicion of advanced disease (5 or 15.6%) and failure to progress (5 or 15.6%). Patients requiring conversion were older and had a higher Charlson score (both p <0.01), including an increased prevalence of chronic kidney disease (p = 0.02). Increasing tumor size (5 vs 3.1 cm, p <0.01) and R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and hilar location) score (9 vs 8, p <0.01) were also associated with an increased risk of conversion. Worse baseline renal function (OR 0.98, 95% CI 0.96-0.99, p = 0.04), large tumor size (OR 1.44, 95% CI 1.22-1.7, p <0.01) and increasing R.E.N.A.L. score (p = 0.02) were independent predictors of conversion. Compared to converted cases, at latest followup standard robotic partial nephrectomy cases had similar short-term oncologic outcomes but better renal functional preservation (p <0.01). At a high volume center the rate of robotic partial nephrectomy conversion to radical nephrectomy was 3.1%, including 2.2% of preoperatively anticipated nephrectomy cases. Increasing tumor size and complexity, and poor preoperative renal function are the main predictors of conversion. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Post-Discharge Worsening Renal Function in Patients with Type 2 Diabetes and Recent Acute Coronary Syndrome.

PubMed

Morici, Nuccia; Savonitto, Stefano; Ponticelli, Claudio; Schrieks, Ilse C; Nozza, Anna; Cosentino, Francesco; Stähli, Barbara E; Perrone Filardi, Pasquale; Schwartz, Gregory G; Mellbin, Linda; Lincoff, A Michael; Tardif, Jean-Claude; Grobbee, Diederick E

2017-09-01

Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge worsening renal function has never been investigated in this setting. We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure. Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval [CI], 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001). Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

Atherosclerotic renal artery stenosis in the post-CORAL era part 1: the renal penumbra concept and next-generation functional diagnostic imaging.

PubMed

Sag, Alan Alper; Inal, Ibrahim; Okcuoglu, John; Rossignol, Patrick; Ortiz, Alberto; Afsar, Baris; Sos, Thomas A; Kanbay, Mehmet

2016-04-01

After three neutral trials in which renal artery stenting failed to improve renal function or reduce cardiovascular and renal events, the controversy surrounding diagnosis and treatment of atherosclerotic renal artery stenosis and renovascular hypertension has led to paradigm shifts in the diagnostic algorithm. Noninvasive determination of earlier events (cortex hypoxia and renal artery hemodynamic changes) will supersede late sequelae (calcific stenosis, renal cortical thinning). Therefore, this review proposes the concept of renal penumbra in defining at-risk ischemic renal parenchyma. The complex field of functional renal magnetic resonance imaging will be reviewed succinctly in a clinician-directed fashion. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery.

PubMed

Stafford-Smith, Mark; Podgoreanu, Mihai; Swaminathan, Madhav; Phillips-Bute, Barbara; Mathew, Joseph P; Hauser, Elizabeth H; Winn, Michelle P; Milano, Carmelo; Nielsen, Dahlia M; Smith, Mike; Morris, Richard; Newman, Mark F; Schwinn, Debra A

2005-03-01

Post-cardiac surgery renal dysfunction is a common, serious, multifactorial disorder, with interpatient variability predicted poorly by preoperative clinical, procedural, and biological markers. Therefore, we tested the hypothesis that selected gene variants are associated with acute renal injury, reflected by a serum creatinine level increase after cardiac surgery. One thousand six hundred seventy-one patients undergoing aortocoronary surgery were studied. Clinical covariates were recorded. DNA was isolated from preoperative blood; mass spectrometry was used for genotype analysis. A model was developed relating clinical and genetic factors to postoperative acute renal injury. A race effect was found; therefore, Caucasians and African Americans were analyzed separately. Overall, clinical factors alone account poorly for postoperative renal injury, although more so in African Americans than Caucasians. When 12 candidate polymorphisms were assessed, 2 alleles (interleukin 6 -572C and angiotensinogen 842C) showed a strong association with renal injury in Caucasians (P < 0.0001; >50% decrease in renal filtration when they present together). Using less stringent criteria for significance (0.01 > P > 0.001), 4 additional polymorphisms are identified (apolipoproteinE 448C [4], angiotensin receptor1 1166C, and endothelial nitric oxide synthase [eNOS] 894T in Caucasians; eNOS 894T and angiotensin-converting enzyme deletion and insertion in African Americans). Adding genetic to clinical factors resulted in the best model, with overall ability to explain renal injury increasing approximately 4-fold in Caucasians and doubling in African Americans (P < 0.0005). In this study, we identify genetic polymorphisms that collectively provide 2- to 4-fold improvement over preoperative clinical factors alone in explaining post-cardiac surgery renal dysfunction. From a mechanistic perspective, most identified genetic variants are associated with increased renal inflammatory and/or vasoconstrictor responses.

Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

PubMed

Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

2017-01-01

Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

Measuring residual renal function for hemodialysis adequacy: Is there an easier option?

PubMed

Davenport, Andrew

2017-10-01

Most patients starting hemodialysis (HD) have residual renal function. As such, there has been increased interest in starting patients with less frequent and shorter dialysis session times. However, for this incremental approach to be successful, patients require regular monitoring of residual renal function, so that as residual renal function declines, the amount of HD is appropriately increased. Currently most dialysis centers rely on interdialytic urine collections. However, many patients find these inconvenient and there may be marked intrapatient variability due to compliance issues. Thus, alternative markers of residual renal function are required for routine clinical practice. Currently three middle sized molecules; cystatin C, β2 microglobulin, and βtrace protein have been investigated as potential endogenous markers of glomerular filtration. Although none is ideal, combinations of these markers have been proposed to provide a more accurate estimation of glomerular clearance, and in particular cut offs for minimal residual renal function. However, in patients with low levels of residual renal function it remains unclear as to whether the benefits of residual renal function equally apply to glomerular filtration or tubular function. © 2017 International Society for Hemodialysis.

Value of Nephrometry Score Constituents on Perioperative Outcomes and Split Renal Function in Patients Undergoing Minimally Invasive Partial Nephrectomy.

PubMed

Watts, Kara L; Ghosh, Propa; Stein, Solomon; Ghavamian, Reza

2017-01-01

To assess the relationship between individual nephrometry score (NS) constituents (RENAL) on perioperative outcomes and renal function of the surgical kidney in patients undergoing laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy. Two hundred forty-five patients who underwent laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Each renal mass' NS was calculated from preoperative computed tomography imaging. Multivariate regression analysis was used to evaluate the effect of NS variables on perioperative outcomes and change in overall renal function (as estimated by glomerular filtration rate) from preoperative to 1-year postoperative. A cohort analysis assessed the effect of NS variables on change in split renal function of the surgical kidney from pre- to postoperative based on nuclear medicine renal scintigraphy. Tumor radius (R), endophytic nature (E), and nearness to collecting system (N) variables significantly and incrementally predicted a longer operative time and warm ischemia time. Overall renal function based on glomerular filtration rate was not affected by any NS variable. However, percent function of the surgical kidney by renal scintigraphy significantly decreased postoperatively as R and E values increased. R, E, and N were associated with significant changes in warm ischemia time and operative time. R and E were associated with a significant decrease in split renal function of the surgical kidney at 1 year after surgery but not with overall renal function. R, E, and N are the NS constituents most relevant to perioperative outcomes and postoperative differential renal function after partial nephrectomy. Copyright © 2016. Published by Elsevier Inc.

Kidney function and cognitive decline in frail elderly: two faces of the same coin?

PubMed

Coppolino, Giuseppe; Bolignano, Davide; Gareri, Pietro; Ruberto, Carmen; Andreucci, Michele; Ruotolo, Giovanni; Rocca, Maurizio; Castagna, Alberto

2018-06-04

Cognitive and renal impairment are pervasive among elderly frails, a high-risk, geriatric sub-population with peculiar clinical characteristics. In a series of frail individuals with non-advanced chronic kidney disease (CKD), we aimed at assessing the entity of functional, general health and cognitive impairment and the possible relationship between these types of dysfunction and the severity of renal impairment. 2229 geriatric subjects were screened for frailty and CKD. Severity of CKD was assessed by eGFR (CKD-EPI formula). Frailty was established by the Fried Index. Functional, general health and cognitive status were assessed by validated score measures. Final analysis included 271 frail CKD subjects (162 women, 109 men). Mean eGFR was 64.25 ± 25.04 mL/min/1.73 m 2 . Prevalence of mild-to-moderate CKD (stage 3-4) was 44%. Twenty-six percent of patients had severe cognitive impairment, while mild and moderate impairment was found in 7 and 67% of individuals, respectively. All subjects had poor functional and general health status. Cognitive capacities significantly decreased across CKD stages (p for trend < 0.0001). In fully adjusted multivariate analyses, cognitive status remained an independent predictor of eGFR (β = 0.465; p < 0.0001). Mild-to-moderate CKD is highly pervasive among frail elderly individuals and the severity of renal dysfunction is independently correlated with that of cognitive impairment. Future studies are advocated to clarify whether the combination of kidney and mental dysfunction may portend a higher risk of worsen outcomes in this high-risk population.

Validation of a Functional Pyelocalyceal Renal Model for the Evaluation of Renal Calculi Passage While Riding a Roller Coaster.

PubMed

Mitchell, Marc A; Wartinger, David D

2016-10-01

The identification and evaluation of activities capable of dislodging calyceal renal calculi require a patient surrogate or validated functional pyelocalyceal renal model. To evaluate roller coaster facilitation of calyceal renal calculi passage using a functional pyelocalyceal renal model. A previously described adult ureteroscopy and renoscopy simulator (Ideal Anatomic) was modified and remolded to function as a patient surrogate. Three renal calculi of different sizes from the patient who provided the original computed tomographic urograph on which the simulator was based were used. The renal calculi were suspended in urine in the model and taken for 20 rides on the Big Thunder Mountain Railroad roller coaster at Walt Disney World in Orlando, Florida. The roller coaster rides were analyzed using variables of renal calculi volume, calyceal location, model position on the roller coaster, and renal calculi passage. Sixty renal calculi rides were analyzed. Independent of renal calculi volume and calyceal location, front seating on the roller coaster resulted in a passage rate of 4 of 24. Independent of renal calculi volume and calyceal location, rear seating on the roller coaster resulted in a passage rate of 23 of 36. Independent of renal calculi volume in rear seating, calyceal location differed in passage rates, with an upper calyceal calculi passage rate of 100%; a middle calyceal passage rate of 55.6%; and a lower calyceal passage rate of 40.0%. The functional pyelocalyceal renal model serves as a functional patient surrogate to evaluate activities that facilitate calyceal renal calculi passage. The rear seating position on the roller coaster led to the most renal calculi passages.

[Choosing not to dialysis in chronic renal failure in stage V (Renal Failure). Evolution of the characteristics of patients between 1992-1995 and 2000-2003].

PubMed

García García, M; Martínez Ocaña, J C; Rodríguez Jornet, A; Almirall, J; Ponz, E; Ibeas, J; López Alba, T

2007-01-01

The incidence of chronic renal failure increase with the age. The selection of patient to dialysis has been increasing in spite of the high comorbidity. Moreover, in our clinical practice the aged patient is not contraindicated to dialysis. However, in the nephrology clinical practice not all the patients start the treatment with dialysis. OBJECTIVE The aim of our study has been to compare the characteristics of the patients who had not been dialyzed between the periods 1992-1995 and 2000-2003 to analyze the trend of the nephrology clinical practice. Comparative study of the characteristics and the evolution of patients with chronic renal failure in stage V, (renal failure) not incorporated to dialysis in one hospital during four years between the periods the 1992-1995 ( period A) and 2000-2003 (period B). Start dialysis (period A versus period B): 116 patients, age 59.9+15.5 years vs. 229 patients, age 64.0+15.8 years (p<0.05). Non-dialysis (period A versus period B): 38 patients, age 77.5+9.3 years vs. 37 patients, age 81.7+6.2 years (p<0.01). Renal function: serum creatinina 7.4+2.4 mg/dl vs. 5.3+1.2 mg/dl (p<0.001), MDRD estimate glomerular filtration 6.9+2.4 mg/dl ml/min/1.73 m2 vs. 10.0+2.3 ml/min/1.73 m2 (p<0.001). Primary renal disease: unknown etiology 31.5 % vs. 24.3 %, nephroangiosclerosis 23.6 % vs. 32.4 %, diabetes 28.9 % vs. 21.6 %. Functional status: dependent patients 34.2 % vs 83.8 % (p<0.001). The principal reason for non-dialysis were: personal decision: 26.3 % vs. 35.1 %, dementia 15.8 % vs. 29.7 %, brief life expectancy because of serious co-existing diseases 13.1 % vs. 21.7 % and serious chronic illness with inability for themselves care 44.7 % vs. 13.1 %. Comorbid conditions: 2.3+1.0 vs. 3.0+1.5 (p<0.05). Survival: 55+168 days vs. 168+236 days (p<0.001). Most of the patients that don't begin dialysis are elderly together with a poor functional capacity and with more autonomy in their decisions. The identification of patients with renal failure (stage V) was detected early in the last period than in the following one. The conservative management of non-dialyzed uremic patients is a significative nephrology clinical practice due to more survival of those persons.

Does size matter? Kidney transplant donor size determines kidney function among living donors

PubMed Central

Narasimhamurthy, Meenakshi; Smith, Lachlan M.; Machan, Jason T.; Reinert, Steven E.; Gohh, Reginald Y.; Dworkin, Lance D.; Merhi, Basma; Patel, Nikunjkumar; Beland, Michael D.

2017-01-01

Background Kidney donor outcomes are gaining attention, particularly as donor eligibility criteria continue to expand. Kidney size, a useful predictor of recipient kidney function, also likely correlates with donor outcomes. Although donor evaluation includes donor kidney size measurements, the association between kidney size and outcomes are poorly defined. Methods We examined the relationship between kidney size (body surface area-adjusted total volume, cortical volume and length) and renal outcomes (post-operative recovery and longer-term kidney function) among 85 kidney donors using general linear models and time-to-chronic kidney disease data. Results Donors with the largest adjusted cortical volume were more likely to achieve an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 over a median 24-month follow-up than those with smaller cortical volumes (P <0.001), had a shorter duration of renal recovery (1.3–2.2 versus 32.5 days) and started with a higher eGFR at pre-donation (107–110 versus 91 mL/min/1.73 m2) and immediately post-nephrectomy (∼63 versus 50–51 mL/min/1.73 m2). Similar findings were seen with adjusted total volume and length. Conclusions Larger kidney donors were more likely to achieve an eGFR ≥60 mL/min/1.73 m2 with renal recovery over a shorter duration due to higher pre-donation and initial post-nephrectomy eGFRs. PMID:28638611

Tumor necrosis factor-α, kidney function, and hypertension.

PubMed

Mehaffey, Eamonn; Majid, Dewan S A

2017-10-01

Hypertension is considered to be a low-grade inflammatory condition characterized by the presence of various proinflammatory cytokines. Tumor necrosis factor-α (TNF-α) is a constituent of the proinflammatory cytokines that is associated with salt-sensitive hypertension (SSH) and related renal injury. Elevated angiotensin II (ANG II) and other factors such as oxidative stress conditions promote TNF-α formation. Many recent studies have provided evidence that TNF-α exerts a direct renal action by regulating hemodynamic and excretory function in the kidney. The cytokine incites a strong natriuretic response and plays a part in regulation of the intrarenal renin-angiotensin system. The exact mechanistic role of TNF-α in the development of SSH is as yet poorly understood. While TNF-α antagonism has been shown to attenuate hypertensive responses in many hypertensive animal models, contrasting findings demonstrate that the direct systemic administration of TNF-α usually induces hypotensive as well as natriuretic responses, indicating a counterregulatory role of TNF-α in SSH. Differential activities of two cell surface receptors of TNF-α (receptor type 1 and type 2) may explain the contradictory functions of TNF-α in the setting of hypertension. This short review will evaluate ongoing research studies that investigate the action of TNF-α within the kidney and its role as an influential pathophysiological variable in the development of SSH and renal injury. This information may help to develop specific TNF-α receptor targeting as an effective treatment strategy in this clinical condition. Copyright © 2017 the American Physiological Society.

Aortic intimal sarcoma masquerading as bilateral renal artery stenosis.

PubMed

Sethi, Supreet; Pothineni, Naga Krishna; Syal, Gaurav; Ali, Syed Mujtaba; Krause, Michelle W

2013-01-01

Aortic intimal sarcoma is a rare tumor with poor prognosis. The most common manifestations are thromboembolic phenomena and vascular obstruction. We present a case of aortic intimal sarcoma causing bilateral renal artery stenosis which manifested as resistant hypertension and acute kidney inury. Multiple attempts to stent the renal arteries were unsuccessful. Eventually the patient developed acute limb ischemia and oliguric kidney failure as complications of the primary tumor.

Relevance of Changes in Serum Creatinine During a Heart Failure Trial of Decongestive Strategies: Insights From the DOSE Trial.

PubMed

Brisco, Meredith A; Zile, Michael R; Hanberg, Jennifer S; Wilson, F Perry; Parikh, Chirag R; Coca, Steven G; Tang, W H Wilson; Testani, Jeffrey M

2016-10-01

Worsening renal function (WRF) is a common endpoint in decompensated heart failure clinical trials because of associations between WRF and adverse outcomes. However, WRF has not universally been identified as a poor prognostic sign, challenging the validity of WRF as a surrogate endpoint. Our aim was to describe the associations between changes in creatinine and adverse outcomes in a clinical trial of decongestive therapies. We investigated the association between changes in creatinine and the composite endpoint of death, rehospitalization or emergency room visit within 60 days in 301 patients in the Diuretic Optimization Strategies Evaluation (DOSE) trial. WRF was defined as an increase in creatinine >0.3 mg/dL and improvement in renal function (IRF) as a decrease >0.3 mg/dL. When examining linear changes in creatinine from baseline to 72 hours (the coprimary endpoint of DOSE), increasing creatinine was associated with lower risk for the composite outcome (HR = 0.81 per 0.3 mg/dL increase, 95% CI 0.67-0.98, P = .026). Compared with patients with stable renal function (n = 219), WRF (n = 54) was not associated with the composite endpoint (HR = 1.17, 95% CI = 0.77-1.78, P = .47). However, compared with stable renal function, there was a strong relationship between IRF (n = 28) and the composite endpoint (HR = 2.52, 95% CI = 1.57-4.03, P < .001). The coprimary endpoint of the DOSE trial, a linear increase in creatinine, was paradoxically associated with improved outcomes. This was driven by absence of risk attributable to WRF and a strong risk associated with IRF. These results argue against using changes in serum creatinine as a surrogate endpoint in trials of decongestive strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.

PubMed

Jensen, Elisa P; Poulsen, Steen S; Kissow, Hannelouise; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte M

2015-04-15

Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats. Copyright © 2015 the American Physiological Society.

Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure.

PubMed

Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D; Macdougall, Iain C; Ponikowski, Piotr; Lainscak, Mitja

2015-12-01

To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P=0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P=0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number: NCT01829880.

Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

PubMed Central

Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y.; Castoldi, Ângela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

2012-01-01

Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA. PMID:22952850

Evaluation of advanced glycation end products and carbonyl compounds in patients with different conditions of oxidative stress.

PubMed

Lapolla, Annunziata; Reitano, Rachele; Seraglia, Roberta; Sartore, Giovanni; Ragazzi, Eugenio; Traldi, Pietro

2005-07-01

Advanced glycation end products (AGE) and dicarbonyl compounds accumulate in serum and tissues of patients with diabetes and chronic renal failure. Pentosidine, free pentosidine, glyoxal and methylglyoxal have been evaluated in plasma of diabetic patients with poor metabolic control at baseline and after the improvement of glycemic levels, and in plasma and peritoneal dialysate of patients with renal failure before and after 12 h of peritoneal dialysis. In diabetic patients, acceptable metabolic control was unable to normalize levels of pentosidine (after 2 and 10 months), glyoxal and methylglyoxal (after 2 months). In patients with end-stage renal disease, mean values of pentosidine, free pentosidine, glyoxal and methylglyoxal decreased in plasma after dialysis. No pentosidine or free pentosidine were present in the peritoneal dialysate at time 0, but were found after 12 h of peritoneal dialysis; glyoxal and methylglyoxal decreased after 12 h of dialysis. So, glyoxal and methylglyoxal, already present in the dialysis fluid, can react with the peritoneal matrix protein, giving a reason for the gradual loss of peritoneal membrane function often observed in patients undergoing long-term peritoneal dialysis.

The Prognostic Importance of Changes in Renal Function during Treatment for Acute Heart Failure Depends on Admission Renal Function

PubMed Central

Reid, Ryan; Ezekowitz, Justin A.; Brown, Paul M.; McAlister, Finlay A.; Rowe, Brian H.; Braam, Branko

2015-01-01

Background Worsening and improving renal function during acute heart failure have been associated with adverse outcomes but few studies have considered the admission level of renal function upon which these changes are superimposed. Objectives The objective of this study was to evaluate definitions that incorporate both admission renal function and change in renal function. Methods 696 patients with acute heart failure with calculable eGFR were classified by admission renal function (Reduced [R, eGFR<45 ml/min] or Preserved [P, eGFR≥45 ml/min]) and change over hospital admission (worsening [WRF]: eGFR ≥20% decline; stable [SRF]; and improving [IRF]: eGFR ≥20% increase). The primary outcome was all-cause mortality. The prevalence of Pres and Red renal function was 47.8% and 52.2%. The frequency of R-WRF, R-SRF, and R-IRF was 11.4%, 28.7%, and 12.1%, respectively; the incidence of P-WRF, P-SRF, and P-IRF was 5.7%, 35.3%, and 6.8%, respectively. Survival was shorter for patients with R-WRF compared to R-IRF (median survival times 13.9 months (95%CI 7.7–24.9) and 32.5 months (95%CI 18.8–56.1), respectively), resulting in an acceleration factor of 2.3 (p = 0.016). Thus, an increase compared with a decrease in renal function was associated with greater than two times longer survival among patients with Reduced renal function. PMID:26380982

Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal function and after unilateral nephrectomy.

PubMed

Bergner, R; Siegrist, B; Gretz, N; Pohlmeyer-Esch, G; Kränzlin, B

2015-09-01

A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and zoledronate (ZOL), but interpretation of these study results was limited because of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The present study investigated the nephrotoxicity of ibandronate and zoledronate in a 1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in rats with normal and with mildly to moderately impaired renal function. We compared rats with normal renal function (SHAM) and with impaired renal function after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg, zoledronate 1mg/kg or placebo once (1×) or nine (9×) times. Renal function and markers of tubular toxicity were measured over a 27 week period. After last bisphosphonate treatment the rats were sacrificed and kidneys examined histologically. All bisphosphonate treated animals showed a significant tubular toxicity, which was temporary except in the ZOL-UNX-9×-group. Also the renal function was only transiently reduced except in the ZOL-UNX-9×-group. Histologically, bisphosphonate treatment led to cortical tubuloepithelial degeneration/necrosis and medullary tubuloepithelial swelling which were slightly more pronounced in ibandronate treated animals, when compared to zoledronate treated animals, especially with impaired renal function. In contrast to the previous study we found a similar nephrotoxicity of ibandronate and zoledronate in rats with normal renal function. In rats with impaired renal function the peak of toxicity had not even been fully reached until end of experiment in the zoledronate treated animals. The peak of toxicity seems to be more severe and delayed in rats with impaired renal function compared with rats with normal renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study.

PubMed

Weir, Matthew A; Gomes, Tara; Mamdani, Muhammad; Juurlink, David N; Hackam, Daniel G; Mahon, Jeffrey L; Jain, Arsh K; Garg, Amit X

2011-06-01

Little evidence justifies the avoidance of glyburide in patients with impaired renal function. We aimed to determine if renal function modifies the risk of hypoglycaemia among patients using glyburide. We conducted a nested case-control study using administrative records and laboratory data from Ontario, Canada. We included outpatients 66 years of age and older with diabetes mellitus and prescriptions for glyburide, insulin or metformin. We ascertained hypoglycaemic events using administrative records and estimated glomerular filtration rates (eGFR) using serum creatinine concentrations. From a cohort of 19,620 patients, we identified 204 cases whose eGFR was ≥ 60 mL/min/1.73 m(2) (normal renal function) and 354 cases whose eGFR was < 60 mL/min/1.73 m(2) (impaired renal function). Compared to metformin, glyburide is associated with a greater risk of hypoglycaemia in patients with both normal [adjusted odds ratio (OR) 9.0, 95% confidence interval (95% CI) 4.9-16.4] and impaired renal function (adjusted OR 6.0, 95% CI 3.8-9.5). We observed a similar relationship when comparing insulin to metformin; the risk was greater in patients with normal renal function (adjusted OR 18.7, 95% CI 10.5-33.5) compared to those with impaired renal function (adjusted OR 7.9, 95% CI 5.0-12.4). Tests of interaction showed that among glyburide users, renal function did not significantly modify the risk of hypoglycaemia, but among insulin users, impaired renal function is associated with a lower risk. In this population-based study, impaired renal function did not augment the risk of hypoglycaemia associated with glyburide use.

Multimarker assessment for the prediction of renal function improvement after percutaneous revascularization for renal artery stenosis.

PubMed

Staub, Daniel; Partovi, Sasan; Zeller, Thomas; Breidthardt, Tobias; Kaech, Max; Boeddinghaus, Jasper; Puelacher, Christian; Nestelberger, Thomas; Aschwanden, Markus; Mueller, Christian

2016-06-01

Identifying patients likely to have improved renal function after percutaneous transluminal renal angioplasty and stenting (PTRA) for renal artery stenosis (RAS) is challenging. The purpose of this study was to use a comprehensive multimarker assessment to identify those patients who would benefit most from correction of RAS. In 127 patients with RAS and decreased renal function and/or hypertension referred for PTRA, quantification of hemodynamic cardiac stress using B-type natriuretic peptide (BNP), renal function using estimated glomerular filtration rate (eGFR), parenchymal renal damage using resistance index (RI), and systemic inflammation using C-reactive protein (CRP) were performed before intervention. Predefined renal function improvement (increase in eGFR ≥10%) at 6 months occurred in 37% of patients. Prognostic accuracy as quantified by the area under the receiver-operating characteristics curve for the ability of BNP, eGFR, RI and CRP to predict renal function improvement were 0.59 (95% CI, 0.48-0.70), 0.71 (95% CI, 0.61-0.81), 0.52 (95% CI, 0.41-0.65), and 0.56 (95% CI, 0.44-0.68), respectively. None of the possible combinations increased the accuracy provided by eGFR (lower eGFR indicated a higher likelihood for eGFR improvement after PTRA, P=ns for all). In the subgroup of 56 patients with pre-interventional eGFR <60 mL/min/1.73 m(2), similar findings were obtained. Quantification of renal function, but not any other pathophysiologic signal, provides at least moderate accuracy in the identification of patients with RAS in whom PTRA will improve renal function.

Review of Herbal Traditional Chinese Medicine for the Treatment of Diabetic Nephropathy

PubMed Central

Sun, Guang-dong; Li, Chao-yuan; Cui, Wen-peng; Guo, Qiao-yan; Dong, Chang-qing; Zou, Hong-bin; Liu, Shu-jun; Dong, Wen-peng; Miao, Li-ning

2016-01-01

Diabetic nephropathy (DN) is the most serious chronic complications of diabetes; 20–40% of diabetic patients develop into end stage renal disease (ESRD). However, exact pathogenesis of DN is not fully clear and we have great difficulties in curing DN; poor treatment of DN led to high chances of mortality worldwide. A lot of western medicines such as ACEI and ARB have been demonstrated to protect renal function of DN but are not enough to delay or retard the progression of DN; therefore, exploring exact and feasible drug is current research hotspot in medicine. Traditional Chinese medicine (TCM) has been widely used to treat and control diabetes and its complications such as DN in a lot of scientific researches, which will give insights into the mechanism of DN, but they are not enough to reveal all the details. In this paper, we summarize the applications of herbal TCM preparations, single herbal TCM, and/or monomers from herbal TCM in the treatment of DN in the recent 10 years, depicting the renal protective effects and the corresponding mechanism, through which we shed light on the renal protective roles of TCM in DN with a particular focus on the molecular basis of the effect and provide a beneficial supplement to the drug therapy for DN. PMID:26649322

Role of renal urothelium in the development and progression of kidney disease.

PubMed

Carpenter, Ashley R; McHugh, Kirk M

2017-04-01

The clinical and financial impact of chronic kidney disease (CKD) is significant, while its progression and prognosis is variable and often poor. Studies using the megabladder (mgb -/- ) model of CKD show that renal urothelium plays a key role in modulating early injury responses following the development of congenital obstruction. The aim of this review is to examine the role that urothelium has in normal urinary tract development and pathogenesis. We discuss normal morphology of renal urothelium and then examine the role that uroplakins (Upks) play in its development. Histologic, biochemical, and molecular characterization of Upk1b RFP/RFP mice indicated Upk1b expression is essential for normal urinary tract development, apical plaque/asymmetric membrane unit (AUM) formation, and differentiation and functional integrity of the renal urothelium. Our studies provide the first evidence that Upk1b is directly associated with the development of congenital anomalies of the urinary tract (CAKUT), spontaneous age-dependent hydronephrosis, and dysplastic urothelia. These observations demonstrate the importance of proper urothelial differentiation in normal development and pathogenesis of the urinary tract and provide a unique working model to test the hypothesis that the complex etiology associated with CKD is dependent upon predetermined genetic susceptibilities that establish pathogenic thresholds for disease initiation and progression.

Role of Renal Urothelium in the Development and Progression of Kidney Disease

PubMed Central

Carpenter, Ashley R.; McHugh, Kirk M.

2016-01-01

The clinical and financial impact of chronic kidney disease (CKD) is significant, while the progression and prognosis of CKD is variable and often poor. Studies using the megabladder (mgb−/−) model of CKD have shown that renal urothelium plays a key role in modulating the early injury responses following the development of congenital obstruction. The aim of this review is to examine the role that urothelium has in normal urinary tract development and pathogenesis. We discuss normal morphology of renal urothelium and then examine the role that uroplakins (Upks) play in its development. Histologic, biochemical and molecular characterization of Upk1bRFP/RFP mice indicated Upk1b expression is essential for normal urinary tract development, apical plaque/AUM formation and differentiation and functional integrity of the renal urothelium. Our studies provide the first evidence Upk1b is directly associated with the development of congenital anomalies of the urinary tract (CAKUT), spontaneous age-dependent hydronephrosis and dysplastic urothelia. These observations demonstrate the importance of proper urothelial differentiation in the normal development and pathogenesis of the urinary tract, and provide a unique working model to test the hypothesis that the complex etiology associated with CKD is dependent upon predetermined genetic susceptibilities that establish pathogenic thresholds for disease initiation and progression. PMID:27115886

Review of Herbal Traditional Chinese Medicine for the Treatment of Diabetic Nephropathy.

PubMed

Sun, Guang-dong; Li, Chao-yuan; Cui, Wen-peng; Guo, Qiao-yan; Dong, Chang-qing; Zou, Hong-bin; Liu, Shu-jun; Dong, Wen-peng; Miao, Li-ning

2016-01-01

Diabetic nephropathy (DN) is the most serious chronic complications of diabetes; 20-40% of diabetic patients develop into end stage renal disease (ESRD). However, exact pathogenesis of DN is not fully clear and we have great difficulties in curing DN; poor treatment of DN led to high chances of mortality worldwide. A lot of western medicines such as ACEI and ARB have been demonstrated to protect renal function of DN but are not enough to delay or retard the progression of DN; therefore, exploring exact and feasible drug is current research hotspot in medicine. Traditional Chinese medicine (TCM) has been widely used to treat and control diabetes and its complications such as DN in a lot of scientific researches, which will give insights into the mechanism of DN, but they are not enough to reveal all the details. In this paper, we summarize the applications of herbal TCM preparations, single herbal TCM, and/or monomers from herbal TCM in the treatment of DN in the recent 10 years, depicting the renal protective effects and the corresponding mechanism, through which we shed light on the renal protective roles of TCM in DN with a particular focus on the molecular basis of the effect and provide a beneficial supplement to the drug therapy for DN.

A retrospective analysis of laparoscopic partial nephrectomy with segmental renal artery clamping and factors that predict postoperative renal function.

PubMed

Li, Pu; Qin, Chao; Cao, Qiang; Li, Jie; Lv, Qiang; Meng, Xiaoxin; Ju, Xiaobing; Tang, Lijun; Shao, Pengfei

2016-10-01

To evaluate the feasibility and efficiency of laparoscopic partial nephrectomy (LPN) with segmental renal artery clamping, and to analyse the factors affecting postoperative renal function. We conducted a retrospective analysis of 466 consecutive patients undergoing LPN using main renal artery clamping (group A, n = 152) or segmental artery clamping (group B, n = 314) between September 2007 and July 2015 in our department. Blood loss, operating time, warm ischaemia time (WIT) and renal function were compared between groups. Univariable and multivariable linear regression analyses were applied to assess the correlations of selected variables with postoperative glomerular filtration rate (GFR) reduction. Volumetric data and estimated GFR of a subset of 60 patients in group B were compared with GFR to evaluate the correlation between these functional variables and preserved renal function after LPN. The novel technique slightly increased operating time, WIT and intra-operative blood loss (P < 0.001), while it provided better postoperative renal function (P < 0.001) compared with the conventional technique. The blocking method and tumour characteristics were independent factors affecting GFR reduction, while WIT was not an independent factor. Correlation analysis showed that estimated GFR presented better correlation with GFR compared with kidney volume (R(2) = 0.794 cf. R(2) = 0.199) in predicting renal function after LPN. LPN with segmental artery clamping minimizes warm ischaemia injury and provides better early postoperative renal function compared with clamping the main renal artery. Kidney volume has a significantly inferior role compared with eGFR in predicting preserved renal function. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

PubMed

Hueper, Katja; Gueler, Faikah; Bräsen, Jan Hinrich; Gutberlet, Marcel; Jang, Mi-Sun; Lehner, Frank; Richter, Nicolas; Hanke, Nils; Peperhove, Matti; Martirosian, Petros; Tewes, Susanne; Vo Chieu, Van Dai; Großhennig, Anika; Haller, Hermann; Wacker, Frank; Gwinner, Wilfried; Hartung, Dagmar

2015-06-15

Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF. Copyright © 2015 the American Physiological Society.

Renal function monitoring in heart failure – what is the optimal frequency? A narrative review

PubMed Central

Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2017-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication‐based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. PMID:28901643

Cardiorenal Syndrome in Acute Heart Failure: Revisiting Paradigms.

PubMed

Núñez, Julio; Miñana, Gema; Santas, Enrique; Bertomeu-González, Vicente

2015-05-01

Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney. Worsening renal function that occurs in patients with acute heart failure has been classified as cardiorenal syndrome type 1. In this setting, worsening renal function is a common finding and is due to complex, multifactorial, and not fully understood processes involving hemodynamic (renal arterial hypoperfusion and renal venous congestion) and nonhemodynamic factors. Traditionally, worsening renal function has been associated with worse outcomes, but recent findings have revealed mixed and heterogeneous results, perhaps suggesting that the same phenotype represents a diversity of pathophysiological and clinical situations. Interpreting the magnitude and chronology of renal changes together with baseline renal function, fluid overload status, and clinical response to therapy might help clinicians to unravel the clinical meaning of renal function changes that occur during an episode of heart failure decompensation. In this article, we critically review the contemporary evidence on the pathophysiology and clinical aspects of worsening renal function in acute heart failure. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

PubMed

Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

2015-01-01

The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

Interobserver agreement for post mortem renal histopathology and diagnosis of acute tubular necrosis in critically ill patients.

PubMed

Glassford, Neil J; Skene, Alison; Guardiola, Maria B; Chan, Matthew J; Bagshaw, Sean M; Bellomo, Rinaldo; Solez, Kim

2017-12-01

The renal histopathology of critically ill patients dying with acute kidney injury (AKI) in intensive care units of high income countries remains uncertain. Retrospective observational assessment of interobserver agreement in the reporting of renal post mortem histopathology, and the ability of pathologists blinded to the clinical context to independently identify the presence of pre-mortem AKI from digital images of histological sections from 34 critically ill patients dying in teaching hospitals in Australia and Canada. We identified a heterogeneous cohort with a median age of 65 years (interquartile range [IQR], 56.5-77), APACHE II score of 27 (IQR, 19-33), and sepsis as the most common admission diagnosis (12/34; 35%). The most common proximate causes of death were cardiovascular (19/34; 56%) and respiratory (7/34; 21%) failure. AKI was common, with 23 patients (68%) developing RIFLE-F AKI, and 21 patients (62%) receiving renal replacement therapy. Structured reporting for tubular inflammation showed excellent agreement (kappa = 1), but no other subdomain demonstrated better than moderate agreement (kappa < 0.6). Only fair agreement (55.9% of cases; kappa = 0.23) was demonstrated on the diagnosis of moderate to severe acute tubular necrosis (ATN). Pathologist A predicted RIFLE-I or worse AKI with the diagnosis of ATN, with an overall accuracy of 61.8%; pathologist B predicted AKI with an accuracy of 35.3%. Post mortem assessment of the renal histopathology in critically ill patients is neither robust nor reproducible; independent pathologists agree poorly on the diagnosis of ATN, and their structural assessment appears dissociated from ante-mortem renal function.

[Renal denervation a treatment for resistant hypertension: a French experience].

PubMed

Benamer, H; Mylotte, D; Garcia-Alonso, C; Unterseeh, T; Garot, P; Louvard, Y; Lefevre, T; Morice, M-C

2013-12-01

Arterial hypertension is the largest single contributor to global mortality, and is poorly controlled in approximately 50% of patients despite lifestyle and pharmacologic interventions. Randomized clinical trials have demonstrated that catheter-based renal sympathetic denervation reduces blood pressure (BP) in patients with resistant hypertension. We sought to evaluate the efficacy of this novel therapy in "Real World" clinical practice. Consecutive patients with treatment-resistant primary hypertension, as defined as home BP>160 mmHg despite treatment with ≥3 antihypertensive drugs, were selected for denervation following renal artery screening. Ambulatory and home BP monitoring was performed in all patients prior to and following percutaneous renal sympathetic denervation. In total, 35 patients were selected for catheter-based renal sympathetic denervation. The mean age was 63.6 ± 11.7 years, 37.1% were women, 37.1% were diabetic, and 11.4% had renal impairment (GFR<45 mL/min). The basal BP (home or ambulatory) was 179.1 ± 20.75/99.66 ± 19.76 mmHg, despite an average of 4.91 ± 0.98 medications per patient. Successful bilateral sympathetic denervation was performed in 33/35 patients (1 renal artery stenosis on angiography [not ablated], 1 patient with renal artery spasm [unilateral denervation]), with an average 5.9 ± 1.6 ablations per renal artery. No procedural complications occurred. At 6 months, blood pressure was 15.5 ± 22.37/87.76 ± 13.97 mmHg (P<0.01). At 2 years follow-up, systolic blood pressure (ABPM or Home BP) was 143.8 ± 15.30 mmHg (P<0.0001) and diastolic 83.42 ± 12.80 mmHg (P=0.0004). There were no adverse events during follow-up, and no deterioration in renal function was observed. Catheter-based renal denervation is safe and efficacious treatment, which results in significant reductions in blood pressure in patients with treatment-resistant hypertension, stable at 2 years follow-up. These results are applicable to real-world patient populations. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Minimally invasive aortic valve replacement in high risk patient groups

PubMed Central

Lewis, Harriet; Benedetto, Umberto; Caputo, Massimo; Angelini, Gianni; Vohra, Hunaid A.

2017-01-01

Minimally invasive aortic valve replacement (AVR) aims to preserve the sternal integrity and improve postoperative outcomes. In low risk patients, this technique can be achieved with comparable mortality to the conventional approach and there is evidence of possible reduction in intensive care and hospital length of stay, transfusion requirement, renal dysfunction, improved respiratory function and increased patient satisfaction. In this review, we aim to asses if these benefits can be transferred to the high risk patient groups. We therefore, discuss the available evidence for the following high risk groups: elderly patients, re-operative surgery, poor lung function, pulmonary hypertension, obesity, concomitant procedures and high risk score cohorts. PMID:28740685

Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure

PubMed Central

Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D.; Macdougall, Iain C.; Ponikowski, Piotr; Lainscak, Mitja

2015-01-01

Aim To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Methods Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Results Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P = 0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P = 0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Conclusions Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number NCT01829880 PMID:26718759

Renal Function Recovery with Total Artificial Heart Support.

PubMed

Quader, Mohammed A; Goodreau, Adam M; Shah, Keyur B; Katlaps, Gundars; Cooke, Richard; Smallfield, Melissa C; Tchoukina, Inna F; Wolfe, Luke G; Kasirajan, Vigneshwar

2016-01-01

Heart failure patients requiring total artificial heart (TAH) support often have concomitant renal insufficiency (RI). We sought to quantify renal function recovery in patients supported with TAH at our institution. Renal function data at 30, 90, and 180 days after TAH implantation were analyzed for patients with RI, defined as hemodialysis supported or an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m. Between January 2008 and December 2013, 20 of the 46 (43.5%) TAH recipients (age 51 ± 9 years, 85% men) had RI, mean preoperative eGFR of 48 ± 7 ml/min/1.73 m. Renal function recovery was noted at each follow-up interval: increment in eGFR (ml/min/1.73 m) at 30, 90, and 180 days was 21 ± 35 (p = 0.1), 16.5 ± 18 (p = 0.05), and 10 ± 9 (p = 0.1), respectively. Six patients (30%) required preoperative dialysis. Of these, four recovered renal function, one remained on dialysis, and one died. Six patients (30%) required new-onset dialysis. Of these, three recovered renal function and three died. Overall, 75% (15 of 20) of patients' renal function improved with TAH support. Total artificial heart support improved renal function in 75% of patients with pre-existing significant RI, including those who required preoperative dialysis.

Improvement in Renal Function and Symptoms of Patients Treated with Laparoscopic Pyeloplasty for Ureteropelvic Junction Obstruction with Less Than 20% Split Renal Function.

PubMed

Nishi, Morihiro; Matsumoto, Kazumasa; Fujita, Tetsuo; Iwamura, Masatsugu

2016-11-01

To evaluate the efficacy of laparoscopic pyeloplasty (LPP) for lower functioning kidney, we investigated the outcome of this procedure for patients with ureteropelvic junction obstruction with decreased renal function, defined as less than 20% split renal function. Between October 1998 and June 2015, we performed transperitoneal dismembered LPP in 224 patients. Among them, 15 patients with less than 20% split renal function were included in this study. Patient characteristics, perioperative split renal functions, complications, and surgical outcomes were retrospectively investigated. Fourteen of 15 patients had preoperative symptoms, including flank pain in 13 patients and gross hematuria in 1 patient. Preoperative 99mTc-mercaptoacetyltriglycine (MAG3) renogram revealed no response to diuretic injection and median split renal function was 16.5%. Median operative time and blood loss were 170 minutes and 20 mL, respectively. There were no complications during the perioperative period. Postoperative MAG3 renogram at 6 and 12 months after the operation revealed significantly increased split renal function (median: 23.8% and 23.7%, p = 0.001 and 0.008, respectively) and response to diuretic injection in all patients. Preoperative symptoms disappeared and no recurrence was seen during the follow-up period for all patients except for one who experienced flank pain again 4 months after the surgery. He subsequently underwent open pyeloplasty, and flank pain disappeared soon after. LPP for patients with low split renal function and flank pain significantly improved symptoms and split renal functions. Although the long-term clinical effects of LPP are unknown, we recommend performing LPP before considering nephrectomy for patients with lower functioning kidney.

Multimarker assessment for the prediction of renal function improvement after percutaneous revascularization for renal artery stenosis

PubMed Central

Partovi, Sasan; Zeller, Thomas; Breidthardt, Tobias; Kaech, Max; Boeddinghaus, Jasper; Puelacher, Christian; Nestelberger, Thomas; Aschwanden, Markus; Mueller, Christian

2016-01-01

Background Identifying patients likely to have improved renal function after percutaneous transluminal renal angioplasty and stenting (PTRA) for renal artery stenosis (RAS) is challenging. The purpose of this study was to use a comprehensive multimarker assessment to identify those patients who would benefit most from correction of RAS. Methods In 127 patients with RAS and decreased renal function and/or hypertension referred for PTRA, quantification of hemodynamic cardiac stress using B-type natriuretic peptide (BNP), renal function using estimated glomerular filtration rate (eGFR), parenchymal renal damage using resistance index (RI), and systemic inflammation using C-reactive protein (CRP) were performed before intervention. Results Predefined renal function improvement (increase in eGFR ≥10%) at 6 months occurred in 37% of patients. Prognostic accuracy as quantified by the area under the receiver-operating characteristics curve for the ability of BNP, eGFR, RI and CRP to predict renal function improvement were 0.59 (95% CI, 0.48–0.70), 0.71 (95% CI, 0.61–0.81), 0.52 (95% CI, 0.41–0.65), and 0.56 (95% CI, 0.44–0.68), respectively. None of the possible combinations increased the accuracy provided by eGFR (lower eGFR indicated a higher likelihood for eGFR improvement after PTRA, P=ns for all). In the subgroup of 56 patients with pre-interventional eGFR <60 mL/min/1.73 m2, similar findings were obtained. Conclusions Quantification of renal function, but not any other pathophysiologic signal, provides at least moderate accuracy in the identification of patients with RAS in whom PTRA will improve renal function. PMID:27280085

Renal function had an independent relationship with coronary artery calcification in Chinese elderly men.

PubMed

Fu, Shihui; Zhang, Zhao; Luo, Leiming; Ye, Ping

2017-04-07

Although previous studies have analyzed the relationship between renal function and coronary artery calcification (CAC) in pre-dialysis and dialysis patients, limited studies have discussed the relationship between renal function and CAC in Chinese elderly men without obvious damage of renal function. The present study was designed to explore the relationship between renal function and CAC in Chinese elderly men without obvious damage of renal function. This cross-sectional study was carried out in 105 male participants older than 60 years with glomerular filtration rate (GFR) ≥ 45 ml/min/1.73 m 2 . CAC was detected by high-definition computerized tomography (HDCT), which is a highly sensitive technique for detecting the CAC and provides the most accurate CAC scores up to date. Age was 72 ± 8.4 years on average and ranged from 60 to 89 years. Simple correlation analysis indicated that all kinds of CAC scores including the Agatston, volume and mass scores inversely correlated with GFR values (p < 0.05 for all). In multivariate linear regression analysis, GFR values were independently associated with all these CAC scores (p < 0.05 for all). Renal function had an independent relationship with CAC detected by HDCT in Chinese elderly men, demonstrating that the relationship between renal function and CAC started at the early stage of renal function decline.

WWSSF - a worldwide study on radioisotopic renal split function: reproducibility of renal split function assessment in children.

PubMed

Geist, Barbara Katharina; Dobrozemsky, Georg; Samal, Martin; Schaffarich, Michael P; Sinzinger, Helmut; Staudenherz, Anton

2015-12-01

The split or differential renal function is the most widely accepted quantitative parameter derived from radionuclide renography. To examine the intercenter variance of this parameter, we designed a worldwide round robin test. Five selected dynamic renal studies have been distributed all over the world by e-mail. Three of these studies are anonymized patient data acquired using the EANM standardized protocol and two studies are phantom studies. In a simple form, individual participants were asked to measure renal split function as well as to provide additional information such as data analysis software, positioning of background region of interest, or the method of calculation. We received the evaluation forms from 34 centers located in 21 countries. The analysis of the round robin test yielded an overall z-score of 0.3 (a z-score below 1 reflecting a good result). However, the z-scores from several centers were unacceptably high, with values greater than 3. In particular, the studies with impaired renal function showed a wide variance. A wide variance in the split renal function was found in patients with impaired kidney function. This study indicates the ultimate importance of quality control and standardization of the measurement of the split renal function. It is especially important with respect to the commonly accepted threshold for significant change in split renal function by 10%.

Fluid Overload is Associated with Late Poor Outcomes in Neonates Following Cardiac Surgery

PubMed Central

Wilder, Nicole S; Yu, Sunkyung; Donohue, Janet E; Goldberg, Caren S; Blatt, Neal B

2016-01-01

Objective Acute kidney injury (AKI) is a severe complication of cardiac surgery associated with increased morbidity and mortality, yet AKI classification for neonates remains challenging. We characterized patterns of post-operative fluid overload (FO) as a surrogate marker for AKI and as a risk factor of poor post-operative outcomes in neonates undergoing cardiac surgery. Design Retrospective cohort study. Setting Single, congenital heart center destination program. Patients 435 neonates undergoing cardiac surgery with cardiopulmonary bypass from January 2006 through December 2010. Interventions None Measurements and Main Results Demographics, diagnosis, and perioperative clinical variables were collected, including daily weights and serum creatinine (SCr) levels. A composite poor clinical outcome (death, need for renal replacement therapy (RRT), or extracorporeal life support (ECLS) within 30 post-operative days) was considered the primary outcome measure. Twenty-one neonates (5%) had a composite poor outcome with 7 (2%) requiring RRT, 8 (2%) requiring ECLS, and 14 (3%) dying between 3 and 30 days post-surgery. Neonates with a composite poor outcome had significantly higher maximum FO (>20%) and were slower to diurese. A receiver-operating characteristic curve determined that FO ≥ 16% and SCr ≥ 0.9 on post-operative day 3 were the optimal cutoffs for significant discrimination on the primary outcome (area under the curve = 0.71 and 0.76, respectively). In multivariable analysis, FO ≥ 16% (adjusted odds ratio [AOR] = 3.7) and SCr ≥ 0.9 (AOR = 6.6) on post-operative day 3 remained an independent risk factor for poor outcome. FO ≥ 16% was also significantly associated with cardiac arrest requiring cardiopulmonary resuscitation, prolonged intensive care unit stay, and chest re-exploration. Conclusions This study highlights the importance of monitoring fluid balance in the neonatal cardiac surgical population, and suggests that daily FO, a readily-available, non-invasive marker of renal function, may be a sensitive and specific predictor of adverse outcomes. PMID:27028790

Tubular damage and worsening renal function in chronic heart failure.

PubMed

Damman, Kevin; Masson, Serge; Hillege, Hans L; Voors, Adriaan A; van Veldhuisen, Dirk J; Rossignol, Patrick; Proietti, Gianni; Barbuzzi, Savino; Nicolosi, Gian Luigi; Tavazzi, Luigi; Maggioni, Aldo P; Latini, Roberto

2013-10-01

This study sought to investigate the relationship between tubular damage and worsening renal function (WRF) in chronic heart failure (HF) BACKGROUND: WRF is associated with poor outcome in chronic HF. It is unclear whether urinary tubular markers may identify patients at risk for WRF. In 2,011 patients with chronic HF, we evaluated the ability of urinary tubular markers (N-acetyl-beta-d-glucosaminidase (NAG), kidney injury molecule (KIM)-1, and neutrophil gelatinase-associated lipocalin (NGAL) to predict WRF. Finally, we assessed the prognostic importance of WRF. A total of 290 patients (14.4%) experienced WRF during follow-up, and WRF was a strong and independent predictor of all-cause mortality and HF hospitalizations (hazard ratio [HR]: 2.87; 95% CI: 2.40 to 3.43; p < 0.001). Patients with WRF had lower baseline glomerular filtration rate and higher KIM-1, NAG, and NGAL levels. In a multivariable-adjusted model, KIM-1 was the strongest independent predictor of WRF (HR: 1.23; 95% CI: 1.09 to 1.39 per log increase; p = 0.001). WRF was associated with strongly impaired outcome in patients with chronic HF. Increased level of urinary KIM-1 was the strongest independent predictor of WRF and could therefore be used to identify patients at risk for WRF and poor clinical outcome. (GISSI-HF-Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic CHF; NCT00336336). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

QT dispersion increases with low glomerular filtration rate in patients with coronary artery disease

PubMed Central

Celik, Murat; Yuksel, UygarCagdas; Gokoglan, Yalcin; Bugan, Baris; Yalcinkaya, Emre; Unal, HilmiUmut; Celik, Turgay; Iyisoy, Atila; Kilic, Selim

2014-01-01

Objective: We aimed to evaluate the relationship between estimated glomerular filtration rate (eGFR) and QT dispersion (QTd) in patients with coronary artery disease (CAD). Methods: Sixty patients(mean age 62.72 ± 12.48 years) included 46 male, (mean age 60.89 ± 12.70 years)and 14 female (mean age 68.71± 9.86 years) were enrolled in this study. Patients were divided into 2 groups according to their eGFR using the 6 variable MDRD equation. Group 1 consisted of patients with estimated eGFR<60 ml/min/1.73m2 and Group 2 consisted of patients witheGFR ≥ 60 ml/min/1.73m2. Results: Baseline patient characteristics were homogeneous in both groups except for age, gender and smoking.Also, the extent of CAD was similar in both groups (p > 0.05) QTd values were found higher in group 1 than those of group 2 (57.23 ± 40.65 ms vs. 31.23 ± 14.47 ms, p = 0.002). After adjustment for age, gender and smoking using one-way ANCOVA test, statistically significant difference in QTd still existedbetween the groups (p=0.038). Conclusion:QTd tends to be higher in patients with poor renal function independent of severity of angiographical CAD. QTd may be a potentially useful non-invasive test in the management of patients with poor renal function, especially those with CAD. PMID:24772124

Renal function monitoring in heart failure - what is the optimal frequency? A narrative review.

PubMed

Al-Naher, Ahmed; Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2018-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication-based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Novel Cancer Therapeutics with Allosteric Modulation of the Mitochondrial C-Raf-DAPK Complex by Raf Inhibitor Combination Therapy.

PubMed

Tsai, Yi-Ta; Chuang, Mei-Jen; Tang, Shou-Hung; Wu, Sheng-Tang; Chen, Yu-Chi; Sun, Guang-Huan; Hsiao, Pei-Wen; Huang, Shih-Ming; Lee, Hwei-Jen; Yu, Cheng-Ping; Ho, Jar-Yi; Lin, Hui-Kuan; Chen, Ming-Rong; Lin, Chung-Chih; Chang, Sun-Yran; Lin, Victor C; Yu, Dah-Shyong; Cha, Tai-Lung

2015-09-01

Mitochondria are the powerhouses of cells. Mitochondrial C-Raf is a potential cancer therapeutic target, as it regulates mitochondrial function and is localized to the mitochondria by its N-terminal domain. However, Raf inhibitor monotherapy can induce S338 phosphorylation of C-Raf (pC-Raf(S338)) and impede therapy. This study identified the interaction of C-Raf with S308 phosphorylated DAPK (pDAPK(S308)), which together became colocalized in the mitochondria to facilitate mitochondrial remodeling. Combined use of the Raf inhibitors sorafenib and GW5074 had synergistic anticancer effects in vitro and in vivo, but targeted mitochondrial function, rather than the canonical Raf signaling pathway. C-Raf depletion in knockout MEF(C-Raf-/-) or siRNA knockdown ACHN renal cancer cells abrogated the cytotoxicity of combination therapy. Crystal structure simulation showed that GW5074 bound to C-Raf and induced a C-Raf conformational change that enhanced sorafenib-binding affinity. In the presence of pDAPK(S308), this drug-target interaction compromised the mitochondrial targeting effect of the N-terminal domain of C-Raf, which induced two-hit damages to cancer cells. First, combination therapy facilitated pC-Raf(S338) and pDAPK(S308) translocation from mitochondria to cytoplasm, leading to mitochondrial dysfunction and reactive oxygen species (ROS) generation. Second, ROS facilitated PP2A-mediated dephosphorylation of pDAPK(S308) to DAPK. PP2A then dissociated from the C-Raf-DAPK complex and induced profound cancer cell death. Increased pDAPK(S308) modification was also observed in renal cancer tissues, which correlated with poor disease-free survival and poor overall survival in renal cancer patients. Besides mediating the anticancer effect, pDAPK(S308) may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation. ©2015 American Association for Cancer Research.

Renal volume assessed by magnetic resonance imaging volumetry correlates with renal function in living kidney donors pre- and postdonation: a retrospective cohort study.

PubMed

Lange, Daniel; Helck, Andreas; Rominger, Axel; Crispin, Alexander; Meiser, Bruno; Werner, Jens; Fischereder, Michael; Stangl, Manfred; Habicht, Antje

2018-07-01

Renal function of potential living kidney donors is routinely assessed with scintigraphy. Kidney anatomy is evaluated by imaging techniques such as magnetic resonance imaging (MRI). We evaluated if a MRI-based renal volumetry is a good predictor of kidney function pre- and postdonation. We retrospectively analyzed the renal volume (RV) in a MRI of 100 living kidney donors. RV was correlated with the tubular excretion rate (TER) of MAG3-scintigraphy, a measured creatinine clearance (CrCl), and the estimated glomerular filtration rate (eGFR) by Cockcroft-Gault (CG), CKD-EPI, and modification of diet in renal disease (MDRD) formula pre- and postdonation during a follow-up of 3 years. RV correlated significantly with the TER (total: r = 0.6735, P < 0.0001). Correlation between RV and renal function was the highest for eGFR by CG (r = 0.5595, P < 0.0001), in comparison with CrCl, MDRD-GFR, and CKD-EPI-GFR predonation. RV significantly correlated with CG-GFR postdonation and predicted CG-GFR until 3 years after donation. MRI renal volumetry might be an alternative technique for the evaluation of split renal function and prediction of renal function postdonation in living kidney donors. © 2018 Steunstichting ESOT.

Impact of high doses of 6% hydroxyethyl starch 130/0.42 and 4% gelatin on renal function in a pediatric animal model.

PubMed

Witt, Lars; Glage, Silke; Lichtinghagen, Ralf; Pape, Lars; Boethig, Dietmar; Dennhardt, Nils; Heiderich, Sebastian; Leffler, Andreas; Sümpelmann, Robert

2016-03-01

Despite serious renal side effects in critically ill adult patients, artificial colloids are still fundamental components of perioperative fluid therapy in infants and children, although the impact of 6% hydroxyethyl starch (HES) and 4% gelatin (GEL) on renal function during pediatric surgery has not been identified yet. To determine the impact of high doses of artificial colloids on renal function, we conducted an experimental animal study and hypothesized that neither the infusion of HES nor of GEL would have a serious impact on renal function. Fifteen sedated piglets were randomly assigned to receive an infusion of either 50 ml · kg(-1) HES or GEL, or a balanced electrolyte solution (crystalloid group). Before and 1 week after infusion, serum and urine renal function tests were recorded and renal biopsies were taken. Serum and urine renal function tests revealed no increase after administration of HES and GEL, and only a discrete increase in serum creatinine (median 9.8 μmol · l(-1), 95% CI 4.0-19.1) in the crystalloid group. Histopathological examination indicated a sparsely, multifocal infiltration of mononuclear cells in all groups and an unspecific pyelectasia of one animal in the GEL group. After high doses of HES or GEL in piglets, no relevant impact on renal function could be found. These results confirm that AKI after HES or GEL is very unlikely in hemodynamically stable perioperative patients with normal renal function. © 2015 John Wiley & Sons Ltd.

Stress and sodium intake in neural control of renal function in hypertension.

PubMed

DiBona, G F

1991-04-01

The interaction between genetic and environmental factors is important in the pathophysiology of hypertension. By examining the effects of two environmental factors--acute psychoemotional stress and dietary sodium intake--in rats with genetic hypertension, an important influence on central neural mechanisms governing the renal sympathetic neural control of renal function has been demonstrated. Additional studies of the central opioid systems have demonstrated an important role of opioid peptides in modulating the renal functional responses to acute psychoemotional stress. The observed renal functional alterations--antidiuresis, antinatriuresis, and renal vasoconstriction--are known to be capable of contributing to the initiation, development, and maintenance of the hypertensive process.

High expression of CXCR4, CXCR7 and SDF-1 predicts poor survival in renal cell carcinoma

PubMed Central

2012-01-01

Background Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The aim of this study was to evaluate the prognostic impact of the expression of the chemokine SDF-1 and its receptors CXCR4 and CXCR7 in patients with renal cell carcinoma. Methods The expression of CXCR4, CXCR7 and SDF-1 in specimens from 97 renal cell carcinoma patients was evaluated by immunohistochemistry on a tissue microarray. These results were correlated with the clinicopathological parameters and survival of the patients. Results CXCR4 and CXCR7 were expressed in all patients, whereas SDF-1 was expressed in 61 patients (62.9%). No association was observed between the expression of CXCR4, CXCR7 or SDF-1 and the clinical or pathological data except between SDF-1 expression and Fuhrman’s grade (P = 0.015). Patients with high expression of CXCR4, CXCR7 and SDF-1 had shorter overall survival and recurrence-free survival than those with low expression. In a multivariate analysis, the high expression of CXCR4, CXCR7 and SDF-1 correlated with poor overall survival and recurrence-free survival independent of gender, age, AJCC stage, lymph node status, metastasis, histologic variant and Fuhrman’s grade. Conclusions High levels of CXCR4, CXCR7 and SDF-1 were associated with poor overall survival and recurrence-free survival in renal cell carcinoma patients. CXCR4, CXCR7 and SDF-1 may serve as useful prognostic markers and therapeutic targets for renal cell carcinoma. PMID:23039915

Cytochrome P450 and Lipoxygenase Metabolites on Renal Function

PubMed Central

Imig, John D.; Hye Khan, Md. Abdul

2018-01-01

Arachidonic acid metabolites have a myriad of biological actions including effects on the kidney to alter renal hemodynamics and tubular transport processes. Cyclooxygenase metabolites are products of an arachidonic acid enzymatic pathway that has been extensively studied in regards to renal function. Two lesser-known enzymatic pathways of arachidonic acid metabolism are the lipoxygenase (LO) and cytochrome P450 (CYP) pathways. The importance of LO and CYP metabolites to renal hemodynamics and tubular transport processes is now being recognized. LO and CYP metabolites have actions to alter renal blood flow and glomerular filtration rate. Proximal and distal tubular sodium transport and fluid and electrolyte homeostasis are also significantly influenced by renal CYP and LO levels. Metabolites of the LO and CYP pathways also have renal actions that influence renal inflammation, proliferation, and apoptotic processes at vascular and epithelial cells. These renal LO and CYP pathway actions occur through generation of specific metabolites and cell-signaling mechanisms. Even though the renal physiological importance and actions for LO and CYP metabolites are readily apparent, major gaps remain in our understanding of these lipid mediators to renal function. Future studies will be needed to fill these major gaps regarding LO and CYP metabolites on renal function. PMID:26756638

Renal perfusion index reflects cardiac systolic function in chronic cardio-renal syndrome.

PubMed

Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

2015-04-17

Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2-4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=-0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation.

The Effect of Patient and Surgical Characteristics on Renal Function After Partial Nephrectomy.

PubMed

Winer, Andrew G; Zabor, Emily C; Vacchio, Michael J; Hakimi, A Ari; Russo, Paul; Coleman, Jonathan A; Jaimes, Edgar A

2018-06-01

The purpose of the study was to identify patient and disease characteristics that have an adverse effect on renal function after partial nephrectomy. We conducted a retrospective review of 387 patients who underwent partial nephrectomy for renal tumors between 2006 and 2014. A line plot with a locally weighted scatterplot smoothing was generated to visually assess renal function over time. Univariable and multivariable longitudinal regression analyses incorporated a random intercept and slope to evaluate the association between patient and disease characteristics with renal function after surgery. Median age was 60 years and most patients were male (255 patients [65.9%]) and white (343 patients [88.6%]). In univariable analysis, advanced age at surgery, larger tumor size, male sex, longer ischemia time, history of smoking, and hypertension were significantly associated with lower preoperative estimated glomerular filtration rate (eGFR). In multivariable analysis, independent predictors of reduced renal function after surgery included advanced age, lower preoperative eGFR, and longer ischemia time. Length of time from surgery was strongly associated with improvement in renal function among all patients. Independent predictors of postoperative decline in renal function include advanced age, lower preoperative eGFR, and longer ischemia time. A substantial number of subjects had recovery in renal function over time after surgery, which continued past the 12-month mark. These findings suggest that patients who undergo partial nephrectomy can experience long-term improvement in renal function. This improvement is most pronounced among younger patients with higher preoperative eGFR. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

PubMed

Corrado, C; Santarelli, M T; Pavlovsky, S; Pizzolato, M

1989-12-01

Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide.

PubMed

Toda, Noboru; Okamura, Tomio

2016-09-01

Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer's disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures.

Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function.

PubMed

DiBona, G F

2000-12-01

Increases in renal sympathetic nerve activity regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. Because increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between the renal sympathetic nerves and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, for example, the direct (by specific innervation) and indirect (by angiotensin II) contributions of increased renal sympathetic nerve activity to the regulation of renal function. The effects of increased renal sympathetic nerve activity on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with ACE inhibitors or angiotensin II-type AT(1)-receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated after renal denervation. These interactions can also be extrarenal, for example, in the central nervous system, wherein renal sympathetic nerve activity and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, whose permeable blood-brain barrier permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II-type AT(1)-receptor antagonists into the ventricular system or microinjected into the rostral ventrolateral medulla are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (eg, congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and renal sympathetic nerve activity are involved in influencing the neural control of renal function.

Acetylator Status Impacts Amifampridine Phosphate (Firdapse™) Pharmacokinetics and Exposure to a Greater Extent Than Renal Function.

PubMed

Haroldsen, Peter E; Sisic, Zlatko; Datt, Joe; Musson, Donald G; Ingenito, Gary

2017-07-01

The purpose of this study is to evaluate safety, tolerability, and pharmacokinetic (PK) properties of amifampridine phosphate (Firdapse™) and its major inactive 3-N-acetyl metabolite in renally impaired and healthy individuals with slow acetylator (SA) and rapid acetylator (RA) phenotypes. This was a Phase I, multicenter, open-label study of the PK properties and safety profile of amifampridine phosphate in individuals with normal, mild, moderate, or severely impaired renal function. Amifampridine phosphate was given as a single 10 mg (base equivalent) dose, and the plasma and urine PK properties of amifampridine and its 3-N-acetyl metabolite were determined. The safety profile was evaluated by monitoring adverse events (AEs), clinical laboratory tests, and physical examinations. Amifampridine clearance was predominantly metabolic through N-acetylation, regardless of renal function in both acetylator phenotypes. In individuals with normal renal function, mean renal clearance represented approximately 3% and 18% of the total clearance of amifampridine in RA and SA, respectively. Large differences in amifampridine exposure were observed between acetylation phenotypes across renal function levels. Mean amifampridine exposure values of AUC 0-∞ and C max were up to 8.8-fold higher in the SA group compared with the RA group across renal function levels. By comparison, mean AUC 0-∞ was less affected by renal function within an acetylator group, only 2- to 3-fold higher in individuals with severe renal impairment (RI) compared with those with normal renal function. Exposure to amifampridine in the SA group with normal renal function was higher (AUC 0-∞, approximately 1.8-fold; C max, approximately 4.1-fold) than the RA group with severe RI. Exposure to the inactive 3-N-acetyl metabolite was higher than amifampridine in both acetylator groups, independent of renal function level. The metabolite is cleared by renal excretion, and exposure was clearly dependent on renal function with 4.0- to 6.8-fold increases in AUC 0-∞ from normal to severe RI. No new tolerability findings were observed. A single dose of 10 mg of amifampridine phosphate was well tolerated, independent of renal function and acetylator status. The results indicate that the PK profile of amifampridine is affected by metabolic acetylator phenotype to a greater extent than by renal function level, supporting Firdapse™ administration in individuals with RI in line with current labeling recommendations. Amifampridine should be dosed to effect per the individual patient need, altering administration frequency and dose in normal through severe RI. The therapeutic dose of amifampridine phosphate should be tailored to the individual patient needs by gradual dose titration up to the present maximum recommended dose (60-80 mg/day) or until dose-limiting AEs intervene to avoid overdosing and underdosing. EudraCT identifier: 2013-005349-35. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Relationship between histopathological changes in post partum renal biopsies and renal function tests of African women with early onset pre-eclampsia.

PubMed

Khedun, S M; Naicker, T; Moodley, J

2000-05-01

To improve the diagnostic accuracy of concurrent renal disease in hypertension of pregnancy, biopsy evaluation is essential. In addition, establishing underlying renal disease is important for prognosis on future pregnancies. We therefore designed a study to determine the diagnostic yield of postpartum renal biopsy and the nature and frequency of complications associated with this procedure. Also, to determine relationships, if any, between renal function tests and ultrastructural and histopathological findings. Fifty renal biopsies were performed in the immediate postpartum period in black African women with early onset pre-eclampsia. Each biopsy specimen was placed in a separate container and coded so that sampling was unknown to the electron microscopist. Each biopsy specimen was divided into three parts, and processed and stained for light, fluorescent and transmission electron microscopy using conventional techniques. Renal tissue biopsies were adequate for diagnostic purposes in all cases. There were no complications in any of the 50 patients studied. Ultrastructural examination confirmed the light microscopy findings. In addition the ultrastructural findings showed intramembranous deposits, foot process fusion and mesangial deposits. In 16 patients with normal renal function tests; the biopsies evaluation from these patients showed ultrastructural changes. In the remaining 34 patients with abnormal renal function tests of varying severity; biopsy evaluation from these patients showed both ultrastructural and histopathological changes. Renal biopsy procedure is safe, and ultrastructural and histological findings obtained from postpartum renal biopsies are more informative than the routine renal function tests.

Renal function decline predicted by left atrial expansion index in non-diabetic cohort with preserved systolic heart function.

PubMed

Hsiao, Shih-Hung; Chiou, Kuan-Rau

2017-05-01

Since natriuretic peptide and troponin are associated with renal prognosis and left atrial (LA) parameters are indicators of subclinical cardiovascular abnormalities, this study investigated whether LA expansion index can predict renal decline. This study analysed 733 (69% male) non-diabetic patients with sinus rhythm, preserved systolic function, and estimated glomerular filtration rate (eGFR) higher than 60 mL/min/1.73 m2. In all patients, echocardiograms were performed and LA expansion index was calculated. Renal function was evaluated annually. The endpoint was a downhill trend in renal function with a final eGFR of <60 mL/min/1.73 m2. Rapid renal decline was defined as an annual decline in eGFR >3 mL/min/1.73 m2. The median follow-up time was 5.2 years, and 57 patients (7.8%) had renal function declines (19 had rapid renal declines, and 38 had incidental renal dysfunction). Events were associated with left ventricular mass index, LA expansion index, and heart failure during the follow-up period. The hazard ratio was 1.426 (95% confidence interval, 1.276-1.671; P < 0.0001) per 10% decrease in LA expansion index and was independently associated with an increased event rate. Compared with the highest quartile for the LA expansion index, the lowest quartile had a 9.7-fold risk of renal function decline in the unadjusted model and a 6.9-fold risk after adjusting for left ventricular mass index and heart failure during the follow-up period. Left atrial expansion index is a useful early indicator of renal function decline and may enable the possibility of early intervention to prevent renal function from worsening. NCT01171040. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Effects of prolonged daily low level mercuric chloride dosing in a horse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, M.C.; Seawright, A.A.

1978-12-01

Relatively few of the signs hitherto accepted as being consistent with chronic inorganic mercury intoxication were exhibited by a horse exposed to 31.3 g inorganic mercury (dose rate 0.4 mg/kg) given as mercuric chloride over 23.5 weeks. Clinical features included poor appetite, weight loss, debility, dullness, transient diarrhea and polydipsia, with little impairment of functional renal capacity. Limited degenerative changes were seen in the renal tubules. Edema and a mild inflammatory infiltrate of predominantly the mucosa and submucosa caused marked thickening of the lower alimentary tract. An approximate mean plasma inorganic mercury concentration of 400 ng/ml was quickly reached andmore » maintained. The kidneys had the highest tissue mercury content, almost 10 times greater than the liver and over 70 times that found in the intestinal mucosa and the dorsal root ganglia. 18 references, 6 figures.« less

Longitudinal changes in kidney parenchymal volume associated with renal artery stenting.

PubMed

Modrall, J Gregory; Timaran, Carlos H; Rosero, Eric B; Chung, Jayer; Plummer, Mitchell; Valentine, R James; Trimmer, Clayton

2012-03-01

This study assessed the longitudinal changes in renal volume after renal artery stenting (RAS) to determine if renal mass is preserved by stenting. The study cohort consisted of 38 patients with longitudinal imaging available for renal volume quantification before and after RAS. Renal volume was estimated as (kidney length) × (width) × (depth/2) based on preoperative renal imaging. For each patient, the clinical response of blood pressure (BP) and renal function to RAS was categorized according to modified American Heart Association guidelines. Changes in renal volume were assessed using paired nonparametric analyses. The cohort was a median age of 69 years (interquartile range [IQR], 60-74 years). A favorable BP response was observed in 11 of 38 patients (28.9%). At a median interval between imaging studies of 21 months (IQR, 13-32 months), ipsilateral renal volume was significantly increased from baseline (146.8 vs 133.8 cm(3);P = .02). This represents a 6.9% relative increase in ipsilateral kidney volume from baseline. A significant negative correlation between preoperative renal volume and the relative change in renal volume postoperatively (r = -0.42; P = .0055) suggests that smaller kidneys experienced the greatest gains in renal volume after stenting. It is noteworthy that the 25 patients with no change in BP or renal function-clinical failures using traditional definitions-experienced a 12% relative increase in ipsilateral renal volume after RAS. Multivariate analysis determined that stable or improved renal volume after stenting was an independent predictor of stable or improved long-term renal function (odds ratio, 0.008; 95% confidence interval, 0.000-0.206; P = .004). These data lend credence to the belief that RAS preserves renal mass in some patients. This benefit of RAS even extends to those patients who would be considered treatment failures by traditional definitions. Patients with stable or increased renal volume after RAS had more stable renal function during long-term follow-up, whereas patients with renal volume loss after stenting were prone to deterioration of renal function. Published by Mosby, Inc.

The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations.

PubMed

Vargas, Félix; Rodríguez-Gómez, Isabel; Vargas-Tendero, Pablo; Jimenez, Eugenio; Montiel, Mercedes

2012-04-01

Thyroid disorders are among the most common endocrine diseases and affect virtually all physiological systems, with an especially marked impact on cardiovascular and renal systems. This review summarizes the effects of thyroid hormones on the renin-angiotensin system (RAS) and the participation of the RAS in the cardiovascular and renal manifestations of thyroid disorders. Thyroid hormones are important regulators of cardiac and renal mass, vascular function, renal sodium handling, and consequently blood pressure (BP). The RAS acts globally to control cardiovascular and renal functions, while RAS components act systemically and locally in individual organs. Various authors have implicated the systemic and local RAS in the mediation of functional and structural changes in cardiovascular and renal tissues due to abnormal thyroid hormone levels. This review analyzes the influence of thyroid hormones on RAS components and discusses the role of the RAS in BP, cardiac mass, vascular function, and renal abnormalities in thyroid disorders.

Changes in Renal Function and Blood Pressure in Patients with Stone Disease

NASA Astrophysics Data System (ADS)

Worcester, Elaine M.

2007-04-01

Stone disease is a rare cause of renal failure, but a history of kidney stones is associated with an increased risk for chronic kidney disease, particularly in overweight patients. Loss of renal function seems especially notable for patients with stones associated with cystinuria, hyperoxaluria, and renal tubular acidosis, in whom the renal pathology shows deposits of mineral obstructing inner medullary collecting ducts, often diffusely. However, even idiopathic calcium oxalate stone formers have a mild but significant decrease in renal function, compared to age, sex and weight-matched normals, and appear to lose renal function with age at a slightly faster rate than non-stone formers. There is also an increased incidence of hypertension among stone formers, although women are more likely to be affected than men.

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus.

PubMed

Sarashina, Akiko; Ueki, Kohjiro; Sasaki, Tomohiro; Tanaka, Yuko; Koiwai, Kazuki; Sakamoto, Wataru; Woerle, Hans J; Salsali, Afshin; Broedl, Uli C; Macha, Sreeraj

2014-11-01

The purpose of this study was to assess the effect of renal impairment on the pharmacokinetic, pharmacodynamic, and safety profiles of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM). In an open-label, parallel-group study, 32 Japanese patients with T2DM and different degrees of renal function (n = 8 per renal function category: normal renal function, estimated glomerular filtration rate [eGFR; Japanese equation] ≥90 mL/min/1.73 m(2); mild renal impairment, eGFR of 60-<90 mL/min/1.73 m(2); moderate renal impairment, eGFR of 30-<60 mL/min/1.73 m(2); and severe renal impairment, eGFR of 15-<30 mL/min/1.73 m(2)) received a single 25 mg dose of empagliflozin. Empagliflozin exposure increased with increasing renal impairment. Maximum empagliflozin plasma concentrations were similar among all renal function groups. Adjusted geometric mean ratios for extent of exposure (AUC0-∞) to empagliflozin versus normal renal function were 128.8% (95% CI, 106.0-156.6%), 143.8% (95% CI, 118.3-174.8%), and 152.3% (95% CI, 125.3-185.2%) for patients with mild, moderate, and severe renal impairment, respectively. Decreases in renal clearance of empagliflozin correlated with eGFR. Urinary glucose excretion decreased with increasing renal impairment and correlated with eGFR (adjusted mean [SE] change from baseline: 75.0 [4.84] g, 62.6 [5.75] g, 57.9 [4.86] g, and 23.7 [5.24] g for patients with normal renal function and mild, moderate, and severe renal impairment, respectively). Only 2 patients (6%) had adverse events; both were mild. Pharmacokinetic data suggest that no dose adjustment of empagliflozin is necessary in Japanese patients with T2DM and renal impairment because increases in exposure were <2-fold. Urinary glucose excretion decreased with increasing renal impairment. ClinicalTrials.gov identifier: NCT01581658. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Kang; Rai, Partab; Lan, Xiqian

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic micemore » and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.« less

Aspects of renal function in patients with colorectal cancer in a gastroenterology clinic of a county hospital in Western Romania.

PubMed

Velciov, Silvia; Hoinoiu, B; Hoinoiu, Teodora; Popescu, Alina; Gluhovschi, Cristina; Grădinaru, Oana; Popescu, Mădalină; Moţiu, Flavia; Timar, R; Gluhovschi, G H; Sporea, I

2013-01-01

Colorectal cancer represents the third cause of cancer. Since its detection in due time is important resolution, appropriate monitoring is mandatory. The present study deals with the relationship between colorectal cancer and renal function, as well as other associated risk factors. Chronic kidney disease (CKD) represents a risk factor of cancer, both in non-dialysed patients and especially in dialysed patients and in patients with renal transplant. It can get aggravated with cancer in general and particularly with colorectal cancer, partly related to the toxins that cannot be appropriately eliminated because of renal functional disturbances. At the same time, immunosuppressive therapy used for treating glomerular or secondary nephropathies represents an important risk factor of cancer. Some patients with colorectal cancer were found to present also impaired renal function, a fact whose significance is still little known. The object of the present paper is an analysis of the case records of a clinic of gastroenterology on the relationship between colorectal cancer and renal functional impairment. We found in the patients with colorectal cancer under study a glomerular filtration rate (GFR calculated with the EPI formula) of < 60 ml/min/1.73m2 in 31/180 patients, respectively 17.22% of the cases, a value that is similar to that in specialised literature. We also analysed associated risk factors that could be related to renal function impairment in these patients: age, gender, anaemia, diabetes mellitus and hypertension. These could represent, together with the colorectal cancer of the investigated patients, risk factors affecting on the one hand renal function, and on the other hand, potentially increasing the risk of cancer. Correction of these risk factors would have beneficial effects on patients. The relationship between renal functional impairment, respectively CKD, and colorectal cancer is to be regarded from the point of view of complex reciprocity: the impairment of the renal function is a factor of risk of colorectal cancer and colorectal cancer can influence renal function of these patients. This report of reciprocity based on important pathogenic mechanisms also interrelates with factors of risk consecutive to both renal function impairment and colorectal cancer.

Interaction between renal function and percutaneous edge-to-edge mitral valve repair using MitraClip.

PubMed

Kaneko, Hidehiro; Neuss, Michael; Schau, Thomas; Weissenborn, Jens; Butter, Christian

2017-02-01

MitraClip (MC; Abbott Vascular, Menlo Park, CA, USA) is a treatment option for mitral regurgitation. Renal dysfunction is closely associated with cardiovascular disease. However, the influence of renal function in MC remains not fully understood. In this study, we aimed to clarify the association between renal function and MC. We examined 206 consecutive patients who underwent MC and divided patients into 3 groups according to estimated glomerular filtration rate (eGFR), normal eGFR (≥60mL/min/1.73m 2 ) (n=70), mild chronic kidney disease (CKD) (30-59mL/min/1.73m 2 ) (n=106), and severe CKD (<30mL/min/1.73m 2 ) (n=30). N-terminal pro-B type natriuretic peptide (NT-pro BNP) levels increased with decreasing eGFR. Kaplan-Meier curves revealed that the long-term survival rate significantly decreased with eGFR. After adjustment with the covariates, severe CKD was still associated with mortality. Improved renal function was observed in 30% and associated with baseline lower NT-pro BNP levels. Patients with improved renal function had higher chronic phase survival rate. Renal dysfunction is common in MC patients and the survival rate decreased with eGFR in association with increased NT-pro BNP levels. MC may improve renal function in approximately 30% of MC patients. Improved renal function is associated with lower NT-pro BNP levels and results in satisfactory prognosis. These results implies a close association between renal function and MC treatment. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Assessment of renal function and electrolytes in patients with thyroid dysfunction in Addis Ababa, Ethiopia: a cross sectional study.

PubMed

Abebe, Nardos; Kebede, Tedla; Wolde, Mistire

2016-01-01

Studies demonstrated that abnormal thyroid functions may result in decreased or increased kidney size, kidney weight, and affect renal functions. In this regard, studies on the association of abnormal thyroid functions and renal function tests are scarcely found in Ethiopia. To assess renal function and electrolytes in patients with thyroid dysfunction, in Addis Ababa, Ethiopia. Cross sectional study was conducted from March 21/2015-May 27/2015 at Arsho Advanced Medical Laboratory. During the study period, 71 patients with thyroid dysfunction were eligible, and socio demographic data collected by structured questionnaire. Then blood sample was collected for thyroid function tests, renal function and blood electrolyte analysis. The collected data was analyzed by SPSS version 20. ANOVA and binary logistic regression were employed to evaluate the mean deference and associations of thyroid hormone with renal function and electrolyte balances. Among the renal function tests, serum uric acid, and creatinine mean values were significantly decreased in hyperthyroid patients; whereas, eGFR mean value was significantly increased in hyperthyroid study patients (P<0.05). Meanwhile, from the electrolyte measurements made, only the mean serum sodium value was significantly increased in hyperthyroid study participants. Binary logistic regression analysis on the association of thyroid dysfunction with electrolyte balance and renal function tests indicated that serum sodium, creatinine, eGFR values and hyperthyroidism have a statistical significant association at AOR 95% CI of 0.141(0.033-0.593, P=0.008); 16.236(3.481-75.739, P=0.001), and 13.797(3.261-58.67, P=0.001) respectively. The current study reveals, thyroid abnormalities may lead to renal function alterations and also may disturb electrolyte balance. Knowledge of this significant association has worthwhile value for clinicians, to manage their patients' optimally.

Evaluation of the quality and health literacy demand of online renal diet information.

PubMed

Lambert, K; Mullan, J; Mansfield, K; Koukomous, A; Mesiti, L

2017-10-01

Dietary modification is critical in the self-management of chronic kidney disease. The present study describes the accuracy, quality and health literacy demand of renal diet information for adults with kidney disease obtained from the Internet and YouTube (www.youtube.com). A comprehensive content analysis was undertaken in April and July 2015 of 254 eligible websites and 161 YouTube videos. The accuracy of the renal diet information was evaluated by comparing the key messages with relevant evidence-based guidelines for the dietary management of people with kidney disease. The DISCERN tool (www.discern.org.uk) was used to evaluate the quality of the material. Health literacy demand was evaluated using the Patient Education Material Assessment Tool (www.ahrq.gov/professionals/prevention-chronic-care/improve/self-mgmt/pemat/index.html) and seven validated readability calculators. The most frequent renal diet topic found online was generic dietary information for people with chronic kidney disease. The proportion of renal diet information obtained from websites that was accurate was 73%. However, this information was mostly of poor quality with extensive shortcomings, difficult to action and written with a high health literacy demand. By contrast, renal diet information available from YouTube was highly understandable and actionable, although only 18% of the videos were accurate, and a large proportion were of poor quality with extensive shortcomings. The most frequent authors of accurate, good quality, understandable, material were government bodies, dietitians, academic institutions and medical organisations. Renal diet information found online that is written by government bodies, dietitians, academic institutions and medical organisations is recommended. Further work is required to improve the quality and, most importantly, the actionability of renal diet information found online. © 2017 The British Dietetic Association Ltd.

Inhospital and Post-discharge Changes in Renal Function After Transcatheter Aortic Valve Replacement.

PubMed

Blair, John E A; Brummel, Kent; Friedman, Julie L; Atri, Prashant; Sweis, Ranya N; Russell, Hyde; Ricciardi, Mark J; Malaisrie, S Chris; Davidson, Charles J; Flaherty, James D

2016-02-15

The aim of this study was to determine the influence of inhospital and post-discharge worsening renal function (WRF) on prognosis after transcatheter aortic valve replacement (TAVR). Severe chronic kidney disease and inhospital WRF are both associated with poor outcomes after TAVR. There are no data available on post-discharge WRF and outcomes. This was a single-center study evaluating all TAVR from June 1, 2008, to June 31, 2014. WRF was defined as an increase in serum creatinine of ≥0.3 mg/dl. Inhospital WRF was measured from day 0 until discharge or day 7 if the hospitalization was >7 days. Post-discharge WRF was measured at 30 days after discharge. Descriptive statistics, Kaplan-Meier time-to-event analysis, and multivariate logistic regression were used. In a series of 208 patients who underwent TAVR, 204 with complete renal function data were used in the inhospital analysis and 168 who returned for the 30-day follow-up were used in the post-discharge analysis. Inhospital WRF was seen in 28%, whereas post-discharge WRF in 12%. Inhospital and post-discharge WRF were associated with lower rates of survival; however, after multivariate analysis, only post-discharge WRF remained a predictor of 1-year mortality (hazard ratio 1.18, p = 0.030 for every 1 mg/dl increase in serum creatinine). In conclusion, the rate of inhospital WRF is higher than the rate of post-discharge WRF after TAVR, and post-discharge WRF is more predictive of mortality than inhospital WRF. Copyright © 2016 Elsevier Inc. All rights reserved.

Dietary sodium modulation of aldosterone activation and renal function during the progression of experimental heart failure.

PubMed

Miller, Wayne L; Borgeson, Daniel D; Grantham, J Aaron; Luchner, Andreas; Redfield, Margaret M; Burnett, John C

2015-02-01

Aldosterone activation is central to the sodium–fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: (i) high sodium [250 mEq (5.8 g) per day, n =6]; (ii) standard sodium [58 mEq (1.3 g) per day, n =6]; and (iii) sodium restriction [11 mEq (0.25 g) per day, n =6]. During the 38-day study, haemodynamics, renal function, plasma renin activity (PRA), and aldosterone were measured. Changes in haemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups; however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression.

Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients.

PubMed

Moreso, F; Serón, D; Gil-Vernet, S; Riera, L; Fulladosa, X; Ramos, R; Alsina, J; Grinyó, J M

1999-04-01

Transplant recipients of kidneys harvested from old donors have a high incidence of delayed graft function (DGF) and a poor graft outcome. This result is partly explained by the increased incidence of acute rejection in patients suffering from DGF. However, the long-term impact of donor age and DGF in rejection free renal transplants is not well established. The aim of the present work is to evaluate the impact of donor age and DGF on long-term outcome in renal transplants with or without acute rejection. We review all cadaveric kidney transplants performed in our centre between April 1984 and December 1995 treated with a cyclosporin-based immunosuppression. Five hundred and ninety-five patients were included. The overall incidence of DGF was 29.1%, and this event was associated with an increased donor age and cold ischaemia time. Univariate and multivariate analysis showed that graft loss was associated with acute rejection (relative risk (RR) 2.24, 95% confidence interval (CI) 1.62-3.01); DGF (RR 1.83, 95% CI 1.32-2.54); donors >50 years (RR 1.65, 95% CI 1.13-2.38); and retransplantation (RR 1.52, 95% CI 1.01-2.31). In rejection-free patients there were two independent predictors of graft failure: donor >50 years (RR 2.40, 95% CI 1.45-4.01); and DGF (RR 2.42, 95% CI 1.53-3.84). Regardless of the presence of acute rejection, delayed graft function amplifies the detrimental effect of advanced donor age on long-term graft outcome.

Treatment of hepatorenal syndrome as defined by the international ascites club by albumin and furosemide infusion according to the central venous pressure: a prospective pilot study.

PubMed

Péron, Jean-Marie; Bureau, Christophe; Gonzalez, Laurent; Garcia-Ricard, Franck; de Soyres, Olivier; Dupuis, Emmanuel; Alric, Laurent; Pourrat, Jacques; Vinel, Jean-Pierre

2005-12-01

Hepatorenal syndrome (HRS) is a functional renal failure that occurs late during cirrhosis. The prognosis is extremely poor with a mean survival of 1.7 wks from the time of diagnosis. The aim of the present study was to examine the effects of albumin and furosemide administration tailored to central venous pressure (CVP) on renal function and clinical outcome. We treated 20 consecutive patients with HRS. Albumin was given to increase and/or maintain CVP above 3 cm H(2)O. If diuresis remained below 50 mL/h despite effective volume expansion, furosemide was administrated. Patients were considered responders and treatment was discontinued when creatinine clearance rose above 40 mL/min or serum creatinine fell under 132 mumol/L. The need for albumin varied from patient to patient (extremes 40-600 g) and in the same patient from day to day. All but one needed furosemide. Eleven patients (55%) responded to treatment. In this population, diuresis, serum creatinine, and creatinine clearance were all significantly improved. Creatinine clearance at baseline was predictive of treatment efficacy. Survival increased in these patients compared to nonresponders defined as patients with no improvement in renal function (259 days +/- 113 compared to 14 days +/- 3, p < 0.0005). Response to treatment and the type of HRS were the only variables with an independent prognostic value. This study shows that HRS as defined by the International Ascites Club can be treated by albumin administration alone or with furosemide given according to the patient's specific need using CVP.

Reduction of severe mitral regurgitation with the MitraClip system improves renal function in two patients presenting with acute kidney injury and progressive renal failure due to cardio renal syndrome.

PubMed

Asdonk, T; Nickenig, G; Hammerstingl, C

2014-10-01

Mitral regurgitation (MR) is a frequent valve disorder in elderly patients, often accompanied by multiple comorbidities such as renal impairment. In these patients percutaneous mitral valve (MV) repair has become an established treatment option but the role of MR on renal dysfunction is not yet well defined. We here report on two cases presenting with severe MR and progressive renal failure caused by cardio renal syndrome, in which percutaneous MV treatment with the MitraClip system significantly improved renal function. These findings suggest that interventional MV repair can prevent progression of renal deterioration in patients suffering from combined advanced heart and renal failure. Further clinical studies are necessary to support our finding and to answer the question whether optimizing renal function by implantation of the MitraClip device is also of prognostic relevance in these patients. © 2014 Wiley Periodicals, Inc.

Quantitative analysis of the renal aging in rats. Stereological study.

PubMed

Melchioretto, Eduardo Felippe; Zeni, Marcelo; Veronez, Djanira Aparecida da Luz; Martins, Eduardo Lopes; Fraga, Rogério de

2016-05-01

To evaluate the renal function and the renal histological alterations through the stereology and morphometrics in rats submitted to the natural process of aging. Seventy two Wistar rats, divided in six groups. Each group was sacrificed in a different age: 3, 6, 9, 12, 18 and 24 months. It was performed right nephrectomy, stereological and morphometric analysis of the renal tissue (renal volume and weight, density of volume (Vv[glom]) and numerical density (Nv[glom]) of the renal glomeruli and average glomerular volume (Vol[glom])) and also it was evaluated the renal function for the dosage of serum creatinine and urea. There was significant decrease of the renal function in the oldest rats. The renal volume presented gradual increase during the development of the rats with the biggest values registered in the group of animals at 12 months of age and significant progressive decrease in older animals. Vv[glom] presented statistically significant gradual reduction between the groups and the Nv[glom] also decreased significantly. The renal function proved to be inferior in senile rats when compared to the young rats. The morphometric and stereological analysis evidenced renal atrophy, gradual reduction of the volume density and numerical density of the renal glomeruli associated to the aging process.

Examination of the effect of changing to azilsartan from candesartan in renal transplant patients.

PubMed

Ishii, T; Yasuda, M; Saito, Y; Mori, Y; Hayashi, T; Uemura, H; Nose, K; Nishioka, T

2014-01-01

Azilsartan, an angiotensin receptor blocker (ARB), was administered to renal transplant recipients to investigate the safety and antihypertensive effect in addition to its ARB-characteristic organ-protective effect. The subjects were 20 patients (18 males, 2 females; baseline serum creatinine 2.39 ± 1.33 mg/dL) responding poorly to candesartan, who suffered albuminuria (>0.3 g/g creatinine) and hypertension (>140/90 mm Hg) following renal transplantation. Three months after candesartan was switched to azilsartan 20 mg/d, blood pressure, creatinine-corrected urinary albumin excretion, urinary L-type acid binding protein, urinary 8-hydroxydeoxyguano-sine, serum creatinine, and estimated glomerular filtration rate were evaluated. Thirteen patients received cyclosporine (65.0%) and 7 received tacrolimus (35.0%). Another hypertensive (calcium antagonist) agent was combined in 7 (35.0%). Systolic blood pressure significantly decreased from 139.5 mm Hg (baseline) from 128.7 mm Hg (at 3 months), whereas no significant changes were observed for diastolic blood pressure. The percentage of patients achieving the target level of antihypertensive effect (blood pressure < 130/80 mm Hg) significantly improved from 30.0% (baseline) to 70.0% (at 3 months). No significant changes were observed in renal graft function, oxidative stress marker level, or biochemical examination findings. Sufficient antihypertensive effect was demonstrated soon after switching to azilsartan. However, no significant change was found in renal damage markers. Long-term study must be conducted to confirm the protective effect azilsartan on the transplanted kidney, as found with candesartan. The safety of azilsartan was demonstrated. If the transplanted kidney protection is demonstrated, this drug is expected to contribute to the improved long-term prognosis of renal transplant recipients. Copyright © 2014 Elsevier Inc. All rights reserved.

Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic patients with severely impaired renal function.

PubMed

Kitai, Yuichiro; Doi, Yohei; Osaki, Keisuke; Sugioka, Sayaka; Koshikawa, Masao; Sugawara, Akira

2015-12-01

Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function. 125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation. In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month. Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

How botulinum toxin in neurogenic detrusor overactivity can reduce upper urinary tract damage?

PubMed Central

Baron, Maximilien; Grise, Philippe; Cornu, Jean-Nicolas

2016-01-01

Intradetrusor injections of botulinum toxin are the cornerstone of medical treatment of neurogenic detrusor overactivity. The primary aim of this treatment is to ensure a low pressure regimen in the urinary bladder, but the mechanisms leading to long-term protection of the urinary tract remain poorly understood. In this paper, we highlight the potential benefits of intradetrusor injections of botulinum toxin regarding local effects on the bladder structures, urinary tract infections, stone disease, vesico ureteral reflux, hydronephrosis, renal function based on a comprehensive literature review. PMID:26981445

Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers.

PubMed

Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong

2016-01-01

Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60-89 mL/min; N=8), moderate (eCrCl 30-59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration-time curve by 34%, 54%-65%, and 102%, respectively. Lesinurad plasma C max was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment.

[Osteomyelitis and papillary renal adenoma in a red panda (Ailurus fulgens fulgens)].

PubMed

Kummerfeld, M; Knieriem, A; Wohlsein, P

2008-11-01

A 13 year-old female Red Panda (Ailurus fulgens fulgens) kept in a zoological garden was euthanatized due to poor general condition. Pathological examination revealed a chronic bacterial ulcerative to necrotizing dermatitis and osteomyelitis at the lower jaw with subsequent pyogranulomatous pneumonia and diffuse hydropic degeneration of the liver. Additionally, in the kidney a papillary renal adenoma was found. Immunohistochemistry revealed an expression of cytokeratins 8 and/or 19 indicating an origin from the renal tubular epithelium.

Neural regulation of the kidney function in rats with cisplatin induced renal failure

PubMed Central

Goulding, Niamh E.; Johns, Edward J.

2015-01-01

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

Availability of information on renal function in Dutch community pharmacies.

PubMed

Koster, Ellen S; Philbert, Daphne; Noordam, Michelle; Winters, Nina A; Blom, Lyda; Bouvy, Marcel L

2016-08-01

Background Early detection and monitoring of impaired renal function may prevent drug related problems. Objective To assess the availability of information on patient's renal function in Dutch community pharmacies, for patients using medication that might need monitoring in case of renal impairment. Methods Per pharmacy, 25 patients aged ≥65 years using at least one drug that requires monitoring, were randomly selected from the pharmacy information system. For these patients, information on renal function [estimated glomerular filtration rate (eGFR)], was obtained from the pharmacy information system. When absent, this information was obtained from the general practitioner (GP). Results Data were collected for 1632 patients. For 1201 patients (74 %) eGFR values were not directly available in the pharmacy, for another 194 patients (12 %) the eGFR value was not up-to-date. For 1082 patients information could be obtained from the GP, resulting in 942 additional recent eGFR values. Finally, recent information on renal function was available for 72 % (n = 1179) of selected patients. Conclusion In patients using drugs that require renal monitoring, information on renal function is often unknown in the pharmacy. For the majority of patients this information can be retrieved from the GP.

Carotid artery wall shear stress is independently correlated with renal function in the elderly.

PubMed

Guo, Yuqi; Wei, Fang; Wang, Juan; Zhao, Yingxin; Sun, Shangwen; Zhang, Hua; Liu, Zhendong

2018-01-12

Hemodynamic has increasingly been regarded as an important factor of renal function. However, the relationship between carotid artery wall shear stress (WSS) and renal function is not clarified. To investigate the relationship between carotid WSS and renal function, we recruited 761 older subjects aged 60 years and over from community-dwelling in the Shandong area, China. Carotid WSS, endothelial function, and estimated glomerular filtration rate (eGFR) were assessed in all subjects. Subjects were grouped by the interquartile of the carotid artery mean WSS. We found that the eGFRs derived from serum creatinine and/or cystatin C using three CKD-EPI equations were significantly higher and albumin/creatinine ratio was lower in the higher interquartile groups than in the lower interquartile groups ( P <0.05). The mean WSS was independently correlated with eGFRs even after adjustment for confounders. Similar findings were found between carotid artery peak WSS and eGFRs and albumin/creatinine ratio. In addition, we found that endothelial function was strongly related to carotid WSS and renal function after adjustment for confounders. In conclusion, there is an independent correlation of carotid WSS with renal function in the elderly. The local rheologic forces may play an important role in renal function changing. The correlation may be mediated by regulation of endothelial function.

Antihyperglycemic Medication Use Among Medicare Beneficiaries With Heart Failure, Diabetes Mellitus, and Chronic Kidney Disease.

PubMed

Patel, Priyesh A; Liang, Li; Khazanie, Prateeti; Hammill, Bradley G; Fonarow, Gregg C; Yancy, Clyde W; Bhatt, Deepak L; Curtis, Lesley H; Hernandez, Adrian F

2016-07-01

Diabetes mellitus, heart failure (HF), and chronic kidney disease are common comorbidities, but overall use and safety of antihyperglycemic medications (AHMs) among patients with these comorbidities are poorly understood. Using Get With the Guidelines-Heart Failure and linked Medicare Part D data, we assessed AHM use within 90 days of hospital discharge among HF patients with diabetes mellitus discharged from Get With the Guidelines-Heart Failure hospitals between January 1, 2006, and October 1, 2011. We further summarized use by renal function and assessed renal contraindicated AHM use for patients with estimated glomerular filtration rate <30 mL/min/1.73m(2). Among 8791 patients meeting inclusion criteria, the median age was 77 (interquartile range 71-83), 62.3% were female, median body mass index was 29.7 (interquartile range 25.5-35.3), median hemoglobin A1c was 6.8 (interquartile range 6.2-7.8), and 34% had ejection fraction <40%. 74.9% of patients filled a prescription for an AHM, with insulin (39.5%), sulfonylureas (32.4%), and metformin (17%) being the most commonly used AHMs. Insulin use was higher and sulfonylurea/metformin use was lower among patients with lower renal function classes. Among 1512 patients with estimated glomerular filtration rate <30 mL/min/1.73m(2), 35.4% filled prescriptions for renal contraindicated AHMs per prescribing information, though there was a trend toward lower renal contraindicated AHM use over time (Cochran-Mantel-Haenszel row-mean score test P=0.048). Although use of other AHMs was low overall, thiazolidinediones were used in 6.6% of HF patients, and dipeptidyl peptidase-4 inhibitors were used in 5.1%, with trends for decreasing thiazolidinedione use and increased dipeptidyl peptidase-4 inhibitor use over time (P<0.001). Treatment of diabetes mellitus in patients with HF and chronic kidney disease is complex, and these patients are commonly treated with renal contraindicated AHMs, including over 6% receiving a thiazolidinedione, despite known concerns regarding HF. More research regarding safety and efficacy of various AHMs among HF patients is needed. © 2016 American Heart Association, Inc.

Standard pentostatin dose reductions in renal insufficiency are not adequate: selected patients with steroid-refractory acute graft-versus-host disease.

PubMed

Poi, Ming J; Hofmeister, Craig C; Johnston, Jeffrey S; Edwards, Ryan B; Jansak, Buffy S; Lucas, David M; Farag, Sherif S; Dalton, James T; Devine, Steven M; Grever, Michael R; Phelps, Mitch A

2013-08-01

Pentostatin is an irreversible inhibitor of adenosine deaminase and has been used to prevent graft-versus-host disease (GVHD) and to treat both acute and chronic GVHD. Dose reduction equations for patients with renal insufficiency are based on few patients with limited pharmacokinetic and clinical results. This phase II study (NCT00201786) was conducted to assess pentostatin efficacy and infectious complications seen from our previous phase I study in steroid-refractory acute GVHD (aGVHD). Hospitalized patients with steroid-refractory aGVHD were given pentostatin 1.5 mg/m(2)/day intravenously on days 1-3 of each 14-day cycle. Prior to each dose, dose modifications were based on Cockcroft-Gault estimated creatinine clearance (eCrCL) with 30-50 mL/min/1.73 m(2) leading to a 50 % dose reduction and eCrCL less than 30 mL/min/1.73 m(2) leading to study removal. Plasma pentostatin area under the concentration-time curve (AUC) and incidence of infectious complications were evaluated. Two of the eight patients treated demonstrated excessive pentostatin exposure as determined by measurement of AUC. One of these patients had renal impairment, whereas the other patient demonstrated borderline renal function. Despite dose reduction to 0.75 mg/m(2), AUCs were significantly increased compared to the other patients in this study. Seven of eight patients treated with pentostatin had cytomegalovirus (CMV) viremia after pentostatin treatment; however none developed proven CMV disease. A 50 % dose reduction in patients with eCrCL 30-50 mL/min/1.73 m(2) seems reasonable. However, the eCrCL should be interpreted with extreme caution in patients who are critically ill and/or with poor performance status. Renal function assessment based on the Cockcroft-Gault method could be significantly overestimated thus risking pentostatin overdosing. These results imply a need to closely monitor pentostatin exposure in patients with renal insufficiency.

Standard Pentostatin Dose Reductions in Renal Insufficiency are not Adequate: Selected Patients with Steroid-Refractory Acute Graft-versus-Host Disease

PubMed Central

Poi, Ming J.; Hofmeister, Craig C.; Johnston, Jeffrey S.; Edwards, Ryan B.; Jansak, Buffy S.; Lucas, David M.; Farag, Sherif S.; Dalton, James T.; Devine, Steven M.; Grever, Michael R.; Phelps, Mitch A.

2013-01-01

Background and Objective Pentostatin is an irreversible inhibitor of adenosine deaminase and has been used to prevent graft-versus-host disease (GVHD) and to treat both acute and chronic GVHD. Dose reduction equations for patients with renal insufficiency are based on few patients with limited pharmacokinetic and clinical results. This phase II study (NCT00201786) was conducted to assess pentostatin efficacy and infectious complications seen from our previous phase I study in steroid-refractory acute GVHD (aGVHD). Patients and Methods Hospitalized patients with steroid-refractory aGVHD were given pentostatin 1.5 mg/m2/day intravenously on days 1–3 of each 14 day cycle. Prior to each dose, dose modifications were based on Cockcroft-Gault estimated creatinine clearance (eCrCL) with 30–50 ml/min/1.73m2 leading to a 50% dose reduction and eCrCL< 30 ml/min/1.73m2 leading to study removal. Plasma pentostatin area under the concentration-time curve (AUC) and incidence of infectious complications were evaluated. Results Two of the eight patients treated demonstrated excessive pentostatin exposure as determined by measurement of AUC. One of these patients had renal impairment while the other patient demonstrated borderline renal function. Despite dose reduction to 0.75 mg/m2, AUCs were significantly increased compared to the other patients in this study. Seven of eight patients treated with pentostatin had cytomegalovirus (CMV) viremia after pentostatin treatment; however none developed proven CMV disease. Conclusion A 50% dose reduction in patients with eCrCL 30–50 ml/min/1.73m2 seems reasonable. However, the eCrCL should be interpreted with extreme cautions in patients who are critically ill and/or with poor performance status. Renal function assessment based on the Cockcroft-Gault method could be significantly overestimated thus risking pentostatin over-dosing. These results imply a need to closely monitor pentostatin exposure in patients with renal insufficiency. PMID:23588536

Renal complications of lipodystrophy: A closer look at the natural history of kidney disease.

PubMed

Akinci, Baris; Unlu, Sadiye Mehtat; Celik, Ali; Simsir, Ilgin Yildirim; Sen, Sait; Nur, Banu; Keskin, Fatma Ela; Ozgen Saydam, Basak; Kutbay Ozdemir, Nilufer; Sarer Yurekli, Banu; Ergur, Bekir Ugur; Sonmez, Melda; Atik, Tahir; Arslan, Atakan; Demir, Tevfik; Altay, Canan; Tunc, Ulku Aybuke; Arkan, Tugba; Gen, Ramazan; Eren, Erdal; Akinci, Gulcin; Yilmaz, Aslihan Arasli; Bilen, Habib; Ozen, Samim; Celtik, Aygul; Savas Erdeve, Senay; Cetinkaya, Semra; Onay, Huseyin; Sarioglu, Sulen; Oral, Elif Arioglu

2018-07-01

Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. In this multicentre study, prospective follow-up data were collected from 103 subjects with non-HIV-associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR). Kidney volume was measured. Percutaneous renal biopsies were performed in 9 patients. Seventeen of 37 patients with generalized and 29 of 66 patients with partial lipodystrophy had CKD characterized by proteinuria, of those 12 progressed to renal failure subsequently. The onset of renal complications was significantly earlier in patients with generalized lipodystrophy. Patients with CKD were older and more insulin resistant and had worse metabolic control. Increased kidney volume was associated with poor metabolic control and suppressed leptin levels. Renal biopsies revealed thickening of glomerular basal membranes, mesangial matrix abnormalities, podocyte injury, focal segmental sclerosis, ischaemic changes and tubular abnormalities at various levels. Lipid vacuoles were visualized in electron microscopy images. CKD is conspicuously frequent in patients with lipodystrophy which has an early onset. Renal involvement appears multifactorial. While poorly controlled diabetes caused by severe insulin resistance may drive the disease in some cases, inherent underlying genetic defects may also lead to cell autonomous mechanisms contributory to the pathogenesis of kidney disease. © 2018 John Wiley & Sons Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valdez, V.A.; Jacobstein, J.G.

Bone scans were performed with Tc-99m stannous polyphosphate on four patients with thalassemia major. Three of the scans show generalized decrease in skeletal uptake of the radiopharmaceutical, associated with renal enlargement and markedly increased renal radioactivity. The skeletal findings are consistent with the known bone abnormalities in thalassemia major, which are secondary to the extensive marrow hyperplasia and include loss of trabeculae and cortical thinning with consequent loss of bone mass. The increased renal uptake is probably due in part to the increased renal excretion (secondary to the poor bone uptake) and in part to the tubular dilatation and renalmore » enlargement associated with thalassemia major. In addition, the presence of excessive amounts of iron in these patients may play a role in both the skeletal and renal findings.« less

A Review of Anesthetic Effects on Renal Function: Potential Organ Protection.

PubMed

Motayagheni, Negar; Phan, Sheshanna; Eshraghi, Crystal; Nozari, Ala; Atala, Anthony

2017-01-01

Renal protection is a critical concept for anesthesiologists, nephrologists, and urologists, since anesthesia and renal function are highly interconnected and can potentially interfere with one another. Therefore, a comprehensive understanding of anesthetic drugs and their effects on renal function remains fundamental to the success of renal surgeries, especially transplant procedures. Some experimental studies have shown that some anesthetics provide protection against renal ischemia/reperfusion (IR) injury, but there is limited clinical evidence. The effects of anesthetic drugs on renal failure are particularly important in the context of kidney transplantation, since the conditions of preservation following removal profoundly influence the recovery of organ function. Currently, preservation procedures are typically based on the usage of a cold-storage solution. Some anesthetic drugs induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. A more thorough understanding of anesthetic effects on renal function can present a novel approach for developing organ-protective strategies. The aim of this review is to discuss the effects of different anesthetic drugs on renal function, with particular focus on IR injury. Many studies have demonstrated the organ-protective effects of some anesthetic drugs, specifically propofol, which indicate the potential of some anesthetics to introduce novel organ protective targets. This is not surprising, since lipid emulsions are major components of propofol, which accumulating data show provide organ protective effects against IR injury. Key Messages: Thorough understanding of the interaction between anesthetic drugs and renal function remains fundamental to the delivery of safe perioperative care and to optimizing outcomes after renal surgeries, particularly transplant procedures. Anesthetics can be repurposed for organ protection with more information about their effects, especially during transplant procedures. Here, we review the effects of different anesthetic drugs - specifically those that contain lipids in their structure, with special reference to IR injury. © 2017 S. Karger AG, Basel.

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

PubMed

Faisal, Nabiha; Bilodeau, Marc; Aljudaibi, Bandar; Hirch, Geri; Yoshida, Eric M; Hussaini, Trana; Ghali, Maged P; Congly, Stephen E; Ma, Mang M; Lilly, Leslie B

2018-04-04

We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.

Comparing renal function preservation after laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for clinical T1a renal tumor: using a 3D parenchyma measurement system.

PubMed

Zhu, Liangsong; Wu, Guangyu; Huang, Jiwei; Wang, Jianfeng; Zhang, Ruiyun; Kong, Wen; Xue, Wei; Huang, Yiran; Chen, Yonghui; Zhang, Jin

2017-05-01

To compare the renal function preservation between laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy. Data were analyzed from 246 patients who underwent laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for solitary cT1a renal cell carcinoma from January 2013 to July 2015. To reduce the intergroup difference, we used a 1:1 propensity matching analysis. The functional renal parenchyma volume preservation were measured preoperative and 12 months after surgery. The total renal function recovery and spilt GFR was compared. Multivariable logistic analysis was used for predictive factors for renal function decline. After 1:1 propensity matching, each group including 100 patients. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation had a smaller decrease in estimate glomerular filtration rate at 1 day (-7.88 vs -20.01%, p < 0.001), 3 months (-2.31 vs -10.39%, p < 0.001), 6 months (-2.16 vs -7.99%, p = 0.015), 12 months (-3.26 vs -8.03%, p = 0.012) and latest test (-3.24 vs -8.02%, p = 0.040), also had better functional renal parenchyma volume preservation (89.19 vs 84.27%, p < 0.001), lower decrease of the spilt glomerular filtration rate (-9.41 vs -17.13%, p < 0.001) at 12 months. The functional renal parenchyma volume preservation, warm ischemia time and baseline renal function were the important independent factors in determining long-term functional recovery. The laparoscopic radio frequency ablation assisted tumor enucleation technology has unique advantage and potential in preserving renal parenchyma without ischemia damage compared to conventional laparoscopic partial nephrectomy, and had a better outcome, thus we recommend this technique in selected T1a patients.

Influence of percutaneous mitral valve repair using the MitraClip® system on renal function in patients with severe mitral regurgitation.

PubMed

Rassaf, Tienush; Balzer, Jan; Rammos, Christos; Zeus, Tobias; Hellhammer, Katharina; v Hall, Silke; Wagstaff, Rabea; Kelm, Malte

2015-04-01

In patients with mitral regurgitation (MR), changes in cardiac stroke volume, and thus renal preload and afterload may affect kidney function. Percutaneous mitral valve repair (PMVR) with the MitraClip® system can be a therapeutic alternative to surgical valve repair. The influence of MitraClip® therapy on renal function and clinical outcome parameters is unknown. Sixty patients with severe MR underwent PMVR using the MitraClip® system in an open-label observational study. Patients were stratified according to their renal function. All clips have been implanted successfully. Effective reduction of MR by 2-3 grades acutely improved KDOQI class. Lesser MR reduction (MR reduction of 0-1 grades) led to worsening of renal function in patients with pre-existing normal or mild (KDOQI 1-2) compared to severe (KDOQI 3-4) renal dysfunction. Reduction of MR was associated with improvement in Minnesota Living with Heart Failure Questionnaire (MLHFQ), NYHA-stadium, and 6-minute walk test. Successful PMVR was associated with an improvement in renal function. The improvement in renal function was associated with the extent of MR reduction and pre-existing kidney dysfunction. Our data emphasize the relevance of PVMR to stabilize the cardiorenal axis in patients with severe MR. © 2014 Wiley Periodicals, Inc.

Functional Renal Imaging with 2-Deoxy-2-18F-Fluorosorbitol PET in Rat Models of Renal Disorders.

PubMed

Werner, Rudolf A; Wakabayashi, Hiroshi; Chen, Xinyu; Hirano, Mitsuru; Shinaji, Tetsuya; Lapa, Constantin; Rowe, Steven P; Javadi, Mehrbod S; Higuchi, Takahiro

2018-05-01

Precise regional quantitative assessment of renal function is limited with conventional 99m Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2- 18 F-fluorosorbitol ( 18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18 F-FDS is available via simple reduction from routinely used 18 F-FDG. We aimed to further investigate the potential of 18 F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18 F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18 F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99m Tc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18 F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18 F-FDS and 99m Tc-diethylenetriaminepentaacetic acid correlated well with each other ( R = 0.84, P < 0.05). Conclusion: 18 F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18 F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Safety, Tolerability, and Pharmacokinetics of Ribavirin in Hepatitis C Virus-Infected Patients with Various Degrees of Renal Impairment

PubMed Central

Wang, K.; Blotner, S.; Magnusson, M. O.; Wilkins, J. J.; Martin, P.; Solsky, J.; Nieforth, K.; Wat, C.; Grippo, J. F.

2013-01-01

Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV) treatments and many future regimens under investigation. The pharmacokinetics (PK), safety, and tolerability of RBV in chronically HCV-infected patients with renal impairment are not well defined and were the focus of an open-label PK study in HCV-infected patients receiving RBV plus pegylated interferon. Serial RBV plasma samples were collected over 12 h on day 1 of weeks 1 and 12 from patients with moderate renal impairment (creatinine clearance [CLCR], 30 to 50 ml/min; RBV, 600 mg daily), severe renal impairment (CLCR, <30 ml/min; RBV, 400 mg daily), end-stage renal disease (ESRD) (RBV, 200 mg daily), or normal renal function (CLCR, >80 ml/min; RBV, 800 to 1,200 mg daily). Of the 44 patients, 9 had moderately impaired renal function, 10 had severely impaired renal function, 13 had ESRD, and 12 had normal renal function. The RBV dose was reduced because of adverse events (AEs) in 71% and 53% of severe and moderate renal impairment groups, respectively. Despite this modification, patients with moderate and severe impairment had 12-hour (area under the concentration-time curve from 0 to 12 h [AUC0–12]) values 36% (38,452 ng · h/ml) and 25% (35,101 ng · h/ml) higher, respectively, than those with normal renal function (28,192 ng · h/ml). Patients with ESRD tolerated a 200-mg daily dose, and AUC0–12 was 20% lower (22,629 ng · h/ml) than in patients with normal renal function. PK modeling and simulation (M&S) indicated that doses of 200 mg or 400 mg alternating daily for patients with moderate renal impairment and 200 mg daily for patients with severe renal impairment were the most appropriate dose regimens in these patients. PMID:24080649

Diagnostic Performance of CT for Diagnosis of Fat-Poor Angiomyolipoma in Patients With Renal Masses: A Systematic Review and Meta-Analysis.

PubMed

Woo, Sungmin; Suh, Chong Hyun; Cho, Jeong Yeon; Kim, Sang Youn; Kim, Seung Hyup

2017-11-01

The purpose of this article is to systematically review and perform a meta-analysis of the diagnostic performance of CT for diagnosis of fat-poor angiomyolipoma (AML) in patients with renal masses. MEDLINE and EMBASE were systematically searched up to February 2, 2017. We included diagnostic accuracy studies that used CT for diagnosis of fat-poor AML in patients with renal masses, using pathologic examination as the reference standard. Two independent reviewers assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity of included studies were calculated and were pooled and plotted in a hierarchic summary ROC plot. Sensitivity analyses using several clinically relevant covariates were performed to explore heterogeneity. Fifteen studies (2258 patients) were included. Pooled sensitivity and specificity were 0.67 (95% CI, 0.48-0.81) and 0.97 (95% CI, 0.89-0.99), respectively. Substantial and considerable heterogeneity was present with regard to sensitivity and specificity (I 2 = 91.21% and 78.53%, respectively). At sensitivity analyses, the specificity estimates were comparable and consistently high across all subgroups (0.93-1.00), but sensitivity estimates showed significant variation (0.14-0.82). Studies using pixel distribution analysis (n = 3) showed substantially lower sensitivity estimates (0.14; 95% CI, 0.04-0.40) compared with the remaining 12 studies (0.81; 95% CI, 0.76-0.85). CT shows moderate sensitivity and excellent specificity for diagnosis of fat-poor AML in patients with renal masses. When methods other than pixel distribution analysis are used, better sensitivity can be achieved.

Influence of renal impairment on myocardial function in outpatients with systolic heart failure: an echocardiographic and cardiac biomarker study.

PubMed

Bosselmann, Helle; Tonder, Niels; Sölétormos, György; Rossing, Kasper; Iversen, Kasper; Goetze, Jens P; Gustafsson, Finn; Schou, Morten

2014-12-20

Renal dysfunction (RD) is associated with poor outcome in systolic heart failure (HF). Left ventricular ejection fraction (LVEF) is not depressed to a greater extent in patients with RD compared to patients with normal renal function, but it is relatively unknown whether other measures of myocardial function are impaired by RD. The objective of the present study is to evaluate whether RD in systolic HF is associated with excessive impairment of myocardial function, evaluated by strain analysis and cardiac biomarkers. Patients with LVEF <0.45% were enrolled from an outpatient HF clinic. The patients underwent advanced echocardiography. Glomerular filtration rate was estimated by the CKD-EPI equation (eGFR) and patients grouped by eGFR: eGFR group-I, ≥ 90 ml/min/1.73 m(2); eGFR group-II, 60-89 ml/min/1.73 m(2); and eGFR group-III, ≤ 59 ml/min/1.73 m(2). Multivariate regression models were developed to evaluate the associations between eGFR groups, echocardiographic measures and cardiac biomarkers. A total of 149 patients participated in the study. Median age was 69 years, 26% were female; LVEF was 33%. Patients with a low eGFR were older (P < 0.001), but there were no differences in frequency of atrial fibrillation, hypertension, diabetes and ischemic heart disease between eGFR groups (P > 0.05 for all). RD was associated with impaired global longitudinal strain (P = 0.018), increased E/e' (P = 0.032), larger left atria (P = 0.038) and increased levels of proANP (P < 0.001), NT-proBNP (P < 0.001) and troponin I (P = 0.019) after adjustment for traditional confounders. Echocardiographic measures and biomarkers reflecting different aspects of myocardial function are impaired in systolic HF patients with RD and the increased mortality risk in these patients may partly be explained by a depressed cardiac function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Determination of split renal function using dynamic CT-angiography: preliminary results.

PubMed

Helck, Andreas; Schönermarck, Ulf; Habicht, Antje; Notohamiprodjo, Mike; Stangl, Manfred; Klotz, Ernst; Nikolaou, Konstantin; la Fougère, Christian; Clevert, Dirk Andrè; Reiser, Maximilian; Becker, Christoph

2014-01-01

To determine the feasibility of a dynamic CT angiography-protocol with regard to simultaneous assessment of renal anatomy and function. 7 healthy potential kidney donors (58 ± 7 years) underwent a dynamic computed tomography angiography (CTA) using a 128-slice CT-scanner with continuous bi-directional table movement, allowing the coverage of a scan range of 18 cm within 1.75 sec. Twelve scans of the kidneys (n = 14) were acquired every 3.5 seconds with the aim to simultaneously obtain CTA and renal function data. Image quality was assessed quantitatively (HU-measurements) and qualitatively (grade 1-4, 1 = best). The glomerular filtration rate (GFR) was calculated by a modified Patlak method and compared with the split renal function obtained with renal scintigraphy. Mean maximum attenuation was 464 ± 58 HU, 435 ± 48 HU and 277 ± 29 HU in the aorta, renal arteries, and renal veins, respectively. The abdominal aorta and all renal vessels were depicted excellently (grade 1.0). The image quality score for cortex differentiation was 1.6 ± 0.49, for the renal parenchyma 2.4 ± 0.49. GFR obtained from dynamic CTA correlated well with renal scintigraphy with a correlation coefficient of r = 0.84; P = 0.0002 (n = 14). The average absolute deviation was 1.6 mL/min. The average effective dose was 8.96 mSv. Comprehensive assessment of renal anatomy and function is feasible using a single dynamic CT angiography examination. The proposed protocol may help to improve management in case of asymmetric kidney function as well as to simplify evaluation of potential living kidney donors.

Outcome of patients with reactive amyloidosis associated with rheumatoid arthritis in dialysis treatment.

PubMed

Kuroda, Takeshi; Tanabe, Naohito; Sato, Hiroe; Ajiro, Jyunya; Wada, Yoko; Murakami, Syuichi; Hasegawa, Hisashi; Sakatsume, Minoru; Nakano, Masaaki; Gejyo, Fumitake

2006-10-01

The aim was to analyze the clinical outcome of a group of 51 patients diagnosed with systemic amyloidosis associated with rheumatoid arthritis who received hemodialysis (HD) as renal replacement therapy. We monitored the clinical course of the disease and factors that could influence survival. Determination of the onset of the underlying disorder was made retrospectively by reviewing the patient's chart when a diagnosis of amyloid was confirmed. During a 96.9 person-year follow-up, 42 patients died. Survival of these 51 patients from the initiation of HD at 251 days was 50%. Poor prognosis in amyloid patients was mainly due to a large number of sudden deaths immediately following HD therapy. Out of 51 patients 21 needed unplanned initiation of HD. The unplanned initiation was significantly associated with poor survival. Seventy-five percentile of creatinine clearance (Ccr) was 9.7 ml/min, and 75% of these patients who initiated HD had highly impaired renal functional states. These data indicated that amyloidotic patients with HD showed a high mortality rate; therefore, planned initiation of HD was highly recommended to improve the patient's survival. Particular attention was given to the Ccr levels, because the levels of serum creatinine may not be a useful marker for some patients with amyloidosis.

Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy?

PubMed Central

Rasche, F. M.; Rasche, W. G.; Schiekofer, S.; Boldt, A.; Sack, U.; Fahnert, J.

2016-01-01

Summary IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Lifelong mesangial deposition of IgA1 complexes subsist inflammation and nephron loss, but the complex pathogenesis in detail remains unclear. In regard to the heterogeneous course, classical immunosuppressive and specific therapeutic regimens adapted to the loss of renal function will here be discussed in addition to the essential common renal supportive therapy. Renal supportive therapy alleviates secondary, surrogate effects or sequelae on renal function and proteinuria of high intraglomerular pressure and subsequent nephrosclerosis by inhibition of the renin angiotensin system (RAASB). In patients with physiological (ΔGFR < 1·5 ml/min/year) or mild (ΔGFR 1·5–5 ml/min/year) decrease of renal function and proteinuric forms (> 1 g/day after RAASB), corticosteroids have shown a reduction of proteinuria and might protect further loss of renal function. In patients with progressive loss of renal function (ΔGFR > 3 ml/min within 3 months) or a rapidly progressive course with or without crescents in renal biopsy, cyclophosphamide with high‐dose corticosteroids as induction therapy and azathioprine maintenance has proved effective in one randomized controlled study of a homogeneous cohort in loss of renal function (ΔGFR). Mycophenolic acid provided further maintenance in non‐randomized trials. Differentiated, precise, larger, randomized, placebo‐controlled studies focused on the loss of renal function in the heterogeneous forms of IgAN are still lacking. Prospectively, fewer toxic agents will be necessary in the treatment of IgAN. PMID:27283488

Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

PubMed

Berg, Ulla B; Németh, Antal

2018-04-01

On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.

An interdisciplinary consensus on the management of bone metastases from renal cell carcinoma.

PubMed

Grünwald, Viktor; Eberhardt, Berit; Bex, Axel; Flörcken, Anne; Gauler, Thomas; Derlin, Thorsten; Panzica, Martin; Dürr, Hans Roland; Grötz, Knut Achim; Giles, Rachel H; von Falck, Christian; Graser, Anno; Muacevic, Alexander; Staehler, Michael

2018-06-14

Bone is a major site of haematogenous tumour cell spread in renal cell carcinoma (RCC), and most patients with RCC will develop painful and functionally disabling bone metastases at advanced disease stages. The prognosis of these patients is generally poor and the treatment is, therefore, aimed at palliation. However, RCC-associated bone metastases can be curable in select patients. Current data support a multimodal management strategy that includes wide resection of lesions, radiotherapy, systemic therapy, and other local treatment options, which can improve quality of life and survival. Nevertheless, the optimal approach for metastatic bone disease in RCC has not yet been defined and practical recommendations are rare. To improve the management and outcomes of patients with RCC and bone metastases, the International Kidney Cancer Coalition and the interdisciplinary working group on renal tumours of the German Cancer Society convened a meeting of experts with a global perspective to perform an unstructured review and elaborate on current treatment strategies on the basis of published data and expertise. The panel formulated recommendations for the diagnosis and treatment of patients with RCC and metastasis to the bone. Furthermore, the experts summarized current challenges and unmet patient needs that should be addressed in the future.

Impaired left ventricular systolic function and increased brachial-ankle pulse-wave velocity are independently associated with rapid renal function progression.

PubMed

Chen, Szu-Chia; Lin, Tsung-Hsien; Hsu, Po-Chao; Chang, Jer-Ming; Lee, Chee-Siong; Tsai, Wei-Chung; Su, Ho-Ming; Voon, Wen-Chol; Chen, Hung-Chun

2011-09-01

Heart failure and increased arterial stiffness are associated with declining renal function. Few studies have evaluated the association between left ventricular ejection fraction (LVEF) and brachial-ankle pulse-wave velocity (baPWV) and renal function progression. The aim of this study was to assess whether LVEF<40% and baPWV are associated with a decline in the estimated glomerular filtration rate (eGFR) and the progression to a renal end point of ≥25% decline in eGFR. This longitudinal study included 167 patients. The baPWV was measured with an ankle-brachial index-form device. The change in renal function was estimated by eGFR slope. The renal end point was defined as ≥25% decline in eGFR. Clinical and echocardiographic parameters were compared and analyzed. After a multivariate analysis, serum hematocrit was positively associated with eGFR slope, and diabetes mellitus, baPWV (P=0.031) and LVEF<40% (P=0.001) were negatively associated with eGFR slope. Forty patients reached the renal end point. Multivariate, forward Cox regression analysis found that lower serum albumin and hematocrit levels, higher triglyceride levels, higher baPWV (P=0.039) and LVEF<40% (P<0.001) were independently associated with progression to the renal end point. Our results show that LVEF<40% and increased baPWV are independently associated with renal function decline and progression to the renal end point.

Renal function and acute heart failure outcome.

PubMed

Llauger, Lluís; Jacob, Javier; Miró, Òscar

2018-06-05

The interaction between acute heart failure (AHF) and renal dysfunction is complex. Several studies have evaluated the prognostic value of this syndrome. The aim of this systematic review, which includes non-selected samples, was to investigate the impact of different renal function variables on the AHF prognosis. The categories included in the studies reviewed included: creatinine, blood urea nitrogen (BUN), the BUN/creatinine quotient, chronic kidney disease, the formula to estimate the glomerular filtration rate, criteria of acute renal injury and new biomarkers of renal damage such as neutrophil gelatinase-associated lipocalin (NGAL and cystatin c). The basal alterations of the renal function, as well as the acute alterations, transient or not, are related to a worse prognosis in AHF, it is therefore necessary to always have baseline, acute and evolutive renal function parameters. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Predictors of renal and patient outcomes in anti-GBM disease: clinicopathologic analysis of a two-centre cohort.

PubMed

Alchi, Bassam; Griffiths, Meryl; Sivalingam, Murugan; Jayne, David; Farrington, Ken

2015-05-01

Patients with anti-glomerular basement membrane (GBM) disease are at increased risk of morbidity and mortality from renal failure, pulmonary haemorrhage or complications of treatment. One-third also have circulating anti-neutrophil cytoplasmic antibodies (ANCA). The aim of this study was to determine the clinicopathologic predictors of patient and renal outcomes in anti-GBM disease with or without ANCA. Retrospective review of 43 patients diagnosed with anti-GBM disease over 20 years in two centres, including nine with dual anti-GBM and ANCA positivity. Renal biopsies from 27 patients were scored for the presence of active and chronic lesions. Dual-positive patients were almost 20 years older than those with anti-GBM positivity alone (P = 0.003). The overall 1-year patient and renal survivals were 88 and 16%, respectively. Oligoanuria at diagnosis was the strongest predictor of mortality; none of the 16 patients without oligoanuria died. In a Cox regression model excluding oligoanuria, age was the only other independent predictor of survival. Pulmonary haemorrhage and dialysis dependence did not influence mortality. Thirty-five of the forty-three (81%) patients required dialysis at presentation, including all nine dual-positive patients. Of them, only two (5.7%) regained renal function at 1 year. By logistic regression, oligoanuria at diagnosis and percentage of crescents were independent predictors of dialysis independence at 3 months. However, in biopsied patients, the presence of crescents (>75%) added little to the presence of oligoanuria in predicting dialysis independence. Histological activity and chronicity indices did not predict renal outcome. Two of the nine (22%) dual-positive patients relapsed compared with none of the anti-GBM alone patients. Seven patients received kidney transplants without disease recurrence. Oligoanuria is the strongest predictor of patient and renal survival while percentage of glomerular crescents is the only pathologic parameter associated with poor renal outcome in anti-GBM disease. Kidney biopsy may not be necessary in oligoanuric patients without pulmonary haemorrhage. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Variability in the reporting of renal function endpoints in immunosuppression trials in renal transplantation: time for consensus?

PubMed

Knight, Simon R; Hussain, Samia

2016-12-01

Early measures of graft function are increasingly used to assess efficacy in clinical trials of kidney transplant immunosuppression. This study aimed to assess the variability and quality of reporting of these endpoints in contemporary trials. Data regarding renal function endpoints were extracted from 213 reports from randomized controlled trials comparing immunosuppressive interventions in renal transplant recipients published between 2010 and 2014. A total of 174 (81.7%) reports included a measure of renal function; in 44 (20.7%), this was the primary endpoint. A total of 103 manuscripts (48.4%) reported serum creatinine, 142 (66.6%) reported estimated glomerular filtration rate (eGFR), and 26 (12.2%) reported measured GFR. Formulas used for GFR estimation were modification of diet in renal disease (42.3%), Cockroft-Gault (23.5%), Nankivell (15.0%), and CKD-EPI (0.9%). Six studies (2.8%) did not report the formula used to estimate GFR. A total of 13.9% of endpoints had missing data. In 10 studies, disagreement was found in the significance of findings using different measures of renal function. There is a great deal of variability in the reporting of renal function endpoints, with a significant proportion of studies using underperforming or inappropriate estimates. There is a need for consensus as to the best tool for monitoring and reporting renal function post-transplant, and in particular for use in clinical trials and registries. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk factors and co-morbidities associated with changes in renal function among antiretroviral treatment-naïve adults in South Africa: A chart review.

PubMed

Assaram, Shirelle; Mashamba-Thompson, Tivani P; Magula, Nombulelo P

2018-01-01

Our systematic scoping review has demonstrated a research gap in antiretroviral treatment (ART) nephrotoxicity as well as in the long-term outcomes of renal function for patients on ART in South Africa. Bearing in mind the high prevalence of human immunodeficiency virus (HIV) in South Africa, this is of great concern. To determine the risk factors and co-morbidities associated with changes in renal function in HIV-infected adults in South Africa. We conducted a retrospective study of 350 ART-naïve adult patients attending the King Edward VIII HIV clinic, Durban, South Africa. Data were collected at baseline (pre-ART) and at six, 12, 18 and 24 months on ART. Renal function was assessed in the 24-month period using the Modification of Diet in Renal Disease equation and was categorised into normal renal function (estimated glomerular filtration rate [eGFR] ≥ 60), moderate renal impairment (eGFR 30-59), severe renal impairment (eGFR 15-29) and kidney failure (eGFR < 15 mL/min/1.73 m 2 ). Generalised linear models for binary data were used to model the probability of renal impairment over the five time periods, controlling for repeated measures within participants over time. Risk ratios and 95% confidence intervals (CI) were reported for each time point versus baseline. The cohort was 64% female, and 99% were Black. The median age was 36 years. At baseline, 10 patients had hypertension (HPT), six had diabetes, 61 were co-infected with tuberculosis (TB) and 157 patients had a high body mass index (BMI) with 25.4% being categorised as overweight and 19.4% as obese. The majority of the patients (59.3%) were normotensive. At baseline, the majority of the patients (90.4%) had normal renal function (95% CI: 86% - 93%), 7.0% (CI: 5% - 10%) had moderate renal impairment, 1.3% (CI: 0% - 3%) had severe renal impairment and 1.3% (CI: 0% - 3%) had renal failure. As BMI increased by one unit, the risk of renal impairment increased by 1.06 (CI: 1.03-1.10) times. The association of HPT with abnormal renal function was found to be insignificant, p > 0.05. The vast majority of patients were initiated on tenofovir disoproxil fumarate (TDF) (90.6%), in combination with lamivudine (3TC) (100%) and either efavirenz (EFV) (56.6%) or nevirapine (NVP) (43.4%). This study reports a low prevalence of baseline renal impairment in HIV-infected ART-naïve outpatients. An improvement in renal function after the commencement of ART has been demonstrated in this population. However, the long-term outcomes of patients with HIV-related renal disease are not known.

Two distinct clinical courses of renal involvement in rheumatoid patients with AA amyloidosis.

PubMed

Uda, Hiroshi; Yokota, Akira; Kobayashi, Kumiko; Miyake, Tadao; Fushimi, Hiroaki; Maeda, Akira; Saiki, Osamu

2006-08-01

We conducted a prospective study to investigate whether a correlation exists between the clinical course of renal involvement and the pathological findings of renal amyloidosis in patients with rheumatoid arthritis (RA). Patients with RA of more than 5 years' duration and who did not show renal manifestations were selected and received a duodenal biopsy for the diagnosis of amyloidosis. After the diagnosis of AA amyloidosis, patients received a renal biopsy, and patterns of amyloid deposition were examined. We followed the renal functions (serum levels of blood urea nitrogen and creatinine) of patients diagnosed with AA amyloidosis for 5 years. We diagnosed 53 patients with AA amyloidosis and monitored the renal function of 38 of them for > 5 years. The histological patterns were examined; in the 38 patients there were appreciable variations in the patterns of amyloid deposition. In 27 patients, amyloid deposits were found exclusively in the glomerulus (type 1). In the other 11 patients, however, amyloid deposits were found selectively around blood vessels and were totally absent in the glomerulus (type 2). In type 1 patients with glomerular involvement, renal function deteriorated rapidly regardless of disease state; most patients received hemodialysis. In type 2 patients with purely vascular involvement, however, renal function did not deteriorate significantly. In patients with RA and AA amyloidosis, 2 distinct clinical courses in terms of renal involvement were identified. It is suggested that renal function does not deteriorate when amyloid deposition is totally lacking in the glomerulus.

High sodium intake increases blood pressure and alters renal function in intrauterine growth-retarded rats.

PubMed

Sanders, Marijke W; Fazzi, Gregorio E; Janssen, Ger M J; Blanco, Carlos E; De Mey, Jo G R

2005-07-01

A suboptimal fetal environment increases the risk to develop cardiovascular disease in the adult. We reported previously that intrauterine stress in response to reduced uteroplacental blood flow in the pregnant rat limits fetal growth and compromises renal development, leading to an altered renal function in the adult offspring. Here we tested the hypothesis that high dietary sodium intake in rats with impaired renal development attributable to intrauterine stress, results in increased blood pressure, altered renal function, and organ damage. In rats, intrauterine stress was induced by bilateral ligation of the uterine arteries at day 17 of pregnancy. At the age of 12 weeks, the offspring was given high-sodium drinking water (2% sodium chloride). At the age of 16 weeks, rats were instrumented for monitoring of blood pressure and renal function. After intrauterine stress, litter size and birth weight were reduced, whereas hematocrit at birth was increased. Renal blood flow, glomerular filtration rate, and the glomerular filtration fraction were increased significantly after intrauterine stress. High sodium intake did not change renal function and blood pressure in control animals. However, during high sodium intake in intrauterine stress offspring, renal blood flow, glomerular filtration rate, and the filtration fraction were decreased, and blood pressure was increased. In addition, these animals developed severe albuminuria, an important sign of renal dysfunction. Thus, a suboptimal fetal microenvironment, which impairs renal development, results in sodium-dependent hypertension and albuminuria.

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

PubMed

Garcia-Martinez, Rita; Noiret, Lorette; Sen, Sambit; Mookerjee, Rajeshwar; Jalan, Rajiv

2015-02-01

In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P < 0.001). The data suggest that albumin infusion improves renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Aortic calcification burden predicts deterioration of renal function after radical nephrectomy.

PubMed

Fukushi, Ken; Hatakeyama, Shingo; Yamamoto, Hayato; Tobisawa, Yuki; Yoneyama, Tohru; Soma, Osamu; Matsumoto, Teppei; Hamano, Itsuto; Narita, Takuma; Imai, Atsushi; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Terayama, Yuriko; Funyu, Tomihisa; Ohyama, Chikara

2017-02-06

Radical nephrectomy for renal cell carcinoma (RCC) is a risk factor for the development of chronic kidney disease (CKD), and the possibility of postoperative deterioration of renal function must be considered before surgery. We investigated the contribution of the aortic calcification index (ACI) to the prediction of deterioration of renal function in patients undergoing radical nephrectomy. Between January 1995 and December 2012, we performed 511 consecutive radical nephrectomies for patients with RCC. We retrospectively studied data from 109 patients who had regular postoperative follow-up of renal function for at least five years. The patients were divided into non-CKD and pre-CKD based on a preoperative estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m 2 or <60 mL/min/1.73 m 2 , respectively. The ACI was quantitatively measured by abdominal computed tomography before surgery. The patients in each group were stratified between low and high ACIs. Variables such as age, sex, comorbidities, and pre- and postoperative renal function were compared between patients with a low or high ACI in each group. Renal function deterioration-free interval rates were evaluated by Kaplan-Meier analysis. Factors independently associated with deterioration of renal function were determined using multivariate analysis. The median age, preoperative eGFR, and ACI in this cohort were 65 years, 68 mL/min/1.73 m 2 , and 8.3%, respectively. Higher ACI (≥8.3%) was significantly associated with eGFR decline in both non-CKD and pre-CKD groups. Renal function deterioration-free interval rates were significantly lower in the ACI-high than ACI-low strata in both of the non-CKD and pre-CKD groups. Multivariate analysis showed that higher ACI was an independent risk factor for deterioration of renal function at 5 years after radical nephrectomy. Aortic calcification burden is a potential predictor of deterioration of renal function after radical nephrectomy. This study was registered as a clinical trial: UMIN000023577.

Increased curvature of hollow fiber membranes could up-regulate differential functions of renal tubular cell layers.

PubMed

Shen, Chong; Meng, Qin; Zhang, Guoliang

2013-08-01

Tissue engineering devices as in vitro cell culture systems in scaffolds has encountered the bottleneck due to their much lower cell functions than real tissues/organs in vivo. Such situation has been improved in some extent by mimicking the cell microenvironments in vivo from either chemical or physical ways. However, microenvironmental curvature, commonly seen in real tissues/organs, has never been manipulated to regulate the cell performance in vitro. In this regard, this paper fabricated polysulfone membranes with or without polyethylene glycol modification to investigate the impact of curvature on two renal tubular cells. Regardless the varying membrane curvatures among hollow fiber membranes of different diameters and flat membrane of zero curvature, both renal cells could well attach at 4 h of seeding and form similar confluent layers at 6 days on each membrane. Nevertheless, the renal cells on hollow fibers, though showing confluent morphology as those on flat membranes, expressed higher renal functions and, moreover, the renal functions significantly increased with the membrane curvature among hollow fibers. Such upregulation on functions was unassociated with mass transport barrier of hollow fibers, because the cultures on lengthwise cut hollow fibers without mass transfer barrier showed same curvature effect on renal functions as whole hollow fibers. It could be proposed that the curvature of hollow fiber membrane approaching to the large curvature in kidney tubules increased the mechanical stress in the renal cells and thus might up-regulate the renal cell functions. In conclusion, the increase of substrate curvature could up-regulate the cell functions without altering the confluent cell morphology and this finding will facilitate the design of functional tissue engineering devices. Copyright © 2013 Wiley Periodicals, Inc.

Serum osteoprotegerin and renal function in the general population: the Tromsø Study.

PubMed

Vik, Anders; Brodin, Ellen E; Mathiesen, Ellisiv B; Brox, Jan; Jørgensen, Lone; Njølstad, Inger; Brækkan, Sigrid K; Hansen, John-Bjarne

2017-02-01

Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounders were used to study the association between OPG and eGFR. Analyses were stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73 m 2 ) eGFR increased by 0.35 mL/min/1.73 m 2 (95% CI 0.13-0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73 m 2 ), eGFR decreased by 1.54 (95% CI -2.06 to -1.01) per 1 SD increase in serum OPG. OPG was associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function.

Congestive kidney failure in cardiac surgery: the relationship between central venous pressure and acute kidney injury.

PubMed

Gambardella, Ivancarmine; Gaudino, Mario; Ronco, Claudio; Lau, Christopher; Ivascu, Natalia; Girardi, Leonard N

2016-11-01

Acute kidney injury (AKI) in cardiac surgery has traditionally been linked to reduced arterial perfusion. There is ongoing evidence that central venous pressure (CVP) has a pivotal role in precipitating acute renal dysfunction in cardiac medical and surgical settings. We can regard this AKI driven by systemic venous hypertension as 'kidney congestive failure'. In the cardiac surgery population as a whole, when the CVP value reaches the threshold of 14 mmHg in postoperative period, the risk of AKI increases 2-fold with an odds ratio (OR) of 1.99, 95% confidence interval (95% CI) of 1.16-3.40. In cardiac surgery subsets where venous hypertension is a hallmark feature, the incidence of AKI is higher (tricuspid disease 30%, carcinoid valve disease 22%). Even in the non-chronically congested coronary artery bypass population, CVP measured 6 h postoperatively showed significant association to renal failure: risk-adjusted OR for AKI was 5.5 (95% CI 1.93-15.5; P = 0.001) with every 5 mmHg rise in CVP for patients with CVP <9 mmHg; for CVP increments of 5 mmHg above the threshold of 9 mmHg, the risk-adjusted OR for AKI was 1.3 (95% CI 1.01-1.65; P = 0.045). This and other clinical evidence are discussed along with the underlying pathophysiological mechanisms, involving the supremacy of volume receptors in regulating the autonomic output in hypervolaemia, and the regional effect of venous congestion on the nephron. The effect of CVP on renal function was found to be modulated by ventricular function class, aetiology and acuity of venous congestion. Evidence suggests that acute increases of CVP should be actively treated to avoid a deterioration of the renal function, particularly in patients with poor ventricular fraction. Besides, the practice of treating right heart failure with fluid loading should be avoided in favour of other ways to optimize haemodynamics in this setting, because of the detrimental effects on the kidney function. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Renal function preservation with the mTOR inhibitor, Everolimus, after lung transplant.

PubMed

Schneer, Sonia; Kramer, Mordechai R; Fox, Benjamin; Rusanov, Viktoria; Fruchter, Oren; Rosengarten, Dror; Bakal, Ilana; Medalion, Benjamin; Raviv, Yael

2014-06-01

Chronic kidney disease (CKD) is a common complication of calcineurin inhibitors (CNIs) in solid organ transplantation. Previous data suggest that the use of everolimus as an immunosuppressant drug leads to improvement in renal function. The aim of our study was to establish the effect of everolimus in combination with lower doses of CNIs on renal function among lung transplant recipients. Data regarding renal function and pulmonary function were collected from 41 lung transplanted patients in whom treatment was converted to a combination of everolimus with lower doses of CNIs. Patients transferred to everolimus and low dose CNIs showed an improvement in renal function. Patients who continued treatment with everolimus showed improvement in renal function, as opposed to patients who discontinued the treatment. Subjects without proteinuria at baseline showed a better improvement compared with subjects with proteinuria. The incidence of graft rejection did not increase. We concluded that a protocol that includes everolimus and lower doses of CNIs is effective for preserving renal function in lung transplant recipients with CKD. We also believe that an early implementation of everolimus, before proteinuria occurs or creatinine clearance is reduced, could lead to better outcomes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.

PubMed

Hughes, Kim; Flynn, Tanya; de Zoysa, Janak; Dalbeth, Nicola; Merriman, Tony R

2014-02-01

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors.

The impact of neutral-pH peritoneal dialysates with reduced glucose degradation products on clinical outcomes in peritoneal dialysis patients.

PubMed

Cho, Yeoungjee; Johnson, David W; Badve, Sunil V; Craig, Jonathan C; Strippoli, Giovanni F M; Wiggins, Kathryn J

2013-11-01

Neutral-pH peritoneal dialysates, with reduced glucose degradation products (GDPs), have been developed to reduce peritoneal membrane damage. Here our review evaluated the impact of these solutions on clinical outcomes using data from The Cochrane CENTRAL Registry, MEDLINE, Embase, and reference lists for randomized trials of biocompatible solutions. Summary estimates of effect were obtained using a random-effects model of 20 eligible trials encompassing 1383 patients. The quality of studies was generally poor, such that 13 studies had greater than a 20% loss to follow-up and only 3 trials reported adequate concealment of allocation. Use of neutral-pH dialysates with reduced GDPs resulted in larger urine volumes (7 trials; 520 patients; mean difference 126 ml/day, 95% CI 27-226), improved residual renal function after 12 months (6 trials; 360 patients; standardized mean difference 0.31, 95% confidence interval 0.10-0.52), and a trend to reduced inflow pain (1 trial; 58 patients; relative risk 0.51, 95% CI 0.24-1.08). However, there was no significant effect on body weight, hospitalization, peritoneal solute transport rate, peritoneal small-solute clearance, peritonitis, technique failure, patient survival, or adverse events. No significant harms were identified. Thus, based on generally poor quality trials, the use of neutral-pH peritoneal dialysates with reduced GDPs resulted in greater urine volumes and residual renal function after 12 months, but without other clinical benefits. Larger, better-quality studies are needed for accurate evaluation of the impact of these newer dialysates on patient-level hard outcomes.

Effect of bariatric surgery-induced weight loss on renal and systemic inflammation and blood pressure: a 12-month prospective study.

PubMed

Fenske, Wiebke K; Dubb, Sukhpreet; Bueter, Marco; Seyfried, Florian; Patel, Karishma; Tam, Frederick W K; Frankel, Andrew H; le Roux, Carel W

2013-01-01

Bariatric surgery improves arterial hypertension and renal function; however, the underlying mechanisms and effect of different surgical procedures are unknown. In the present prospective study, we compared the 12-month follow-up results after Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, and laparoscopic sleeve gastrectomy on weight loss, hypertension, renal function, and inflammatory status. A total of 34 morbidly obese patients were investigated before, one and 12 months after Roux-en-Y gastric bypass (n = 10), laparoscopic adjustable gastric banding (n = 13), and laparoscopic sleeve gastrectomy (n = 11) for hypertension, kidney function, urinary and serum cytokine levels of macrophage migration inhibitory factor, monocyte chemotactic protein-1, and chemokine ligand-18. At 12 months after surgery, the patients in all 3 treatment arms showed a significant decrease in the mean body mass index, mean arterial pressure, and urinary and serum inflammatory markers (all P < .001). The reduction in urinary and serum cytokine levels correlated directly with body weight loss (P < .05). Patients with impaired renal function at baseline (corresponding to serum cystatin C >.8 mg/L) had a marked improvement in renal function 12 months after surgery (P < .05). Surgically induced weight loss is associated with a marked decrease in renal and systemic inflammation and arterial hypertension and improvement in renal function in patients with pre-existing renal impairment. These effects appear to be independent of surgical procedure. The improvement in renal inflammation could be 1 of the mechanisms contributing to the beneficial effects of bariatric surgery on arterial blood pressure, proteinuria, and renal function. Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Stents in Renal Artery Bifurcation Stenosis: A Case Report

PubMed Central

Leonardou, Polytimi; Pappas, Paris

2011-01-01

A 39-year-old patient presented with poorly controlled hypertension, and she was referred to renal angiogram and potential renal angioplasty. Renal angiogram showed a bifurcation lesion of the right renal artery. A guide wire was used to cross the upper branch, while the lower branch was protected by another same-type guide wire through the same introducer. Two thin monorail balloons were used to dilate the two branches; however, despite balloon dilatation, the stenosis of the vessels persisted. The “kissing balloon” technique was then attempted by simultaneously inflating both branches using the same balloons, but more than a 70% residual stenosis persisted in each branch. Two stents were finally placed in a “kissing” way through the main renal artery. The imaging and clinical results were good, without any procedure-related complications. Three years clinical followup was also good, without any reason for further interventional approach. PMID:21789043

Neural control of renal function: cardiovascular implications.

PubMed

DiBona, G F

1989-06-01

The innervation of the kidney serves to function of its component parts, for example, the blood vessels, the nephron (glomerulus, tubule), and the juxtaglomerular apparatus. Alterations in efferent renal sympathetic nerve activity produce significant changes in renal blood flow, glomerular filtration rate, the reabsorption of water, sodium, and other ions, and the release of renin, prostaglandins, and other vasoactive substances. These functional effects contribute significantly to the renal regulation of total body sodium and fluid volumes with important implications for the control of arterial pressure. The renal nerves, both efferent and afferent, are known to be important contributors to the pathogenesis of hypertension. In addition, the efferent renal nerves participate in the mediation of the excessive renal sodium retention, which characterizes edema-forming states such as congestive heart failure. Thus, the renal nerves play an important role in overall cardiovascular homeostasis in both normal and pathological conditions.

Diagnostic accuracy of calculated serum osmolarity to predict dehydration in older people: adding value to pathology laboratory reports

PubMed Central

Hooper, Lee; Abdelhamid, Asmaa; Ali, Adam; Bunn, Diane K; Jennings, Amy; John, W Garry; Kerry, Susan; Lindner, Gregor; Pfortmueller, Carmen A; Sjöstrand, Fredrik; Walsh, Neil P; Fairweather-Tait, Susan J; Potter, John F; Hunter, Paul R; Shepstone, Lee

2015-01-01

Objectives To assess which osmolarity equation best predicts directly measured serum/plasma osmolality and whether its use could add value to routine blood test results through screening for dehydration in older people. Design Diagnostic accuracy study. Participants Older people (≥65 years) in 5 cohorts: Dietary Strategies for Healthy Ageing in Europe (NU-AGE, living in the community), Dehydration Recognition In our Elders (DRIE, living in residential care), Fortes (admitted to acute medical care), Sjöstrand (emergency room) or Pfortmueller cohorts (hospitalised with liver cirrhosis). Reference standard for hydration status Directly measured serum/plasma osmolality: current dehydration (serum osmolality >300 mOsm/kg), impending/current dehydration (≥295 mOsm/kg). Index tests 39 osmolarity equations calculated using serum indices from the same blood draw as directly measured osmolality. Results Across 5 cohorts 595 older people were included, of whom 19% were dehydrated (directly measured osmolality >300 mOsm/kg). Of 39 osmolarity equations, 5 showed reasonable agreement with directly measured osmolality and 3 had good predictive accuracy in subgroups with diabetes and poor renal function. Two equations were characterised by narrower limits of agreement, low levels of differential bias and good diagnostic accuracy in receiver operating characteristic plots (areas under the curve >0.8). The best equation was osmolarity=1.86×(Na++ K+)+1.15×glucose+urea+14 (all measured in mmol/L). It appeared useful in people aged ≥65 years with and without diabetes, poor renal function, dehydration, in men and women, with a range of ages, health, cognitive and functional status. Conclusions Some commonly used osmolarity equations work poorly, and should not be used. Given costs and prevalence of dehydration in older people we suggest use of the best formula by pathology laboratories using a cutpoint of 295 mOsm/L (sensitivity 85%, specificity 59%), to report dehydration risk opportunistically when serum glucose, urea and electrolytes are measured for other reasons in older adults. Trial registration numbers: DRIE: Research Register for Social Care, 122273; NU-AGE: ClinicalTrials.gov NCT01754012. PMID:26490100

The renal compartment: a hydraulic view.

PubMed

Cruces, Pablo; Salas, Camila; Lillo, Pablo; Salomon, Tatiana; Lillo, Felipe; Hurtado, Daniel E

2014-12-01

The hydraulic behavior of the renal compartment is poorly understood. In particular, the role of the renal capsule on the intrarenal pressure has not been thoroughly addressed to date. We hypothesized that pressure and volume in the renal compartment are not linearly related, similar to other body compartments. The pressure-volume curve of the renal compartment was obtained by injecting fluid into the renal pelvis and recording the rise in intrarenal pressure in six anesthetized and mechanically ventilated piglets, using a catheter Camino 4B® inserted into the renal parenchyma. In healthy kidneys, pressure has a highly nonlinear dependence on the injected volume, as revealed by an exponential fit to the data (R (2) = 0.92). On the contrary, a linear relation between pressure and volume is observed in decapsulated kidneys. We propose a biomechanical model for the renal capsule that is able to explain the nonlinear pressure-volume dependence for moderate volume increases. We have presented experimental evidence and a theoretical model that supports the existence of a renal compartment. The mechanical role of the renal capsule investigated in this work may have important implications in elucidating the role of decompressive capsulotomy in reducing the intrarenal pressure in acutely injured kidneys.

The role of the renal specialist nurse in prevention of renal failure.

PubMed

Hurst, J

2002-01-01

This article will investigate the care required for those with reduced renal function before renal replacement therapy (RRT) commences. Renal nurses are often involved with the technical, monitoring and evaluative aspects of RRT for those with end stage renal failure. However, many patients may experience reduced renal function many years before reaching the stage of needing RRT. Renal nurses are already involved in the preparation of patients for RRT, but are not presently exercising their specialist skills in the period before this time by contributing to the prevention of end stage renal failure (ESRF). Screening programmes carried out in various parts of the world demonstrate that many members of the population have undetected renal insufficiency, and may benefit from intervention from the nephrology team to prevent further renal dysfunction. It is for this group of patients that this article will consider the potential for the renal nurse to expand their scope of practice.

Renal impairment as a surgical indication in primary hyperparathyroidism: do the data support this recommendation?

PubMed

Hendrickson, Chase D; Castro Pereira, Daniel J; Comi, Richard J

2014-08-01

Management of primary hyperparathyroidism has evolved over the past two decades, yet impaired renal function has consistently been a surgical indication. This recommendation has been based upon the historical association between primary hyperparathyroidism and renal impairment, and a review of the literature is needed to determine whether such a recommendation is warranted. PubMed was utilized to identify English-language articles published between January 1990 and February 2014 using keywords related to hyperparathyroidism and renal function. The keywords were "primary hyperparathyroidism," "surgery," "parathyroidectomy," "kidney," "renal," "glomerular filtration rate," and "creatinine." Of the 1926 articles obtained with this search, all articles germane to the topic that quantified the relationship between primary hyperparathyroidism and renal function were included. All references within these articles were investigated for inclusion. When helpful, data tables were constructed to summarize the results succinctly. A secondary elevation of PTH levels has not been consistently shown to occur at the threshold currently indicated for surgical intervention. While renal impairment is seen with more significant disease, mild asymptomatic primary hyperparathyroidism has not been conclusively associated with renal impairment. Furthermore, there is no evidence to suggest that surgically curing primary hyperparathyroidism via a parathyroidectomy has any impact upon renal function.

Effect of renal denervation on dynamic autoregulation of renal blood flow.

PubMed

DiBona, Gerald F; Sawin, Linda L

2004-06-01

Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the renal arterial pressure threshold for steady-state stepwise autoregulation of renal blood flow. This study examined the tonic effect of basal renal sympathetic nerve activity on dynamic autoregulation of renal blood flow in rats with normal (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve activity (congestive heart failure and spontaneously hypertensive rats). Steady-state values of arterial pressure and renal blood flow before and after acute renal denervation were subjected to transfer function analysis. Renal denervation increased basal renal blood flow in congestive heart failure (+35 +/- 3%) and spontaneously hypertensive rats (+21 +/- 3%) but not in Sprague-Dawley and Wistar-Kyoto rats. Renal denervation significantly decreased transfer function gain (i.e., improved autoregulation of renal blood flow) and increased coherence only in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the renal vasculature to oscillations in arterial pressure. Renal denervation increased renal blood flow variability in spontaneously hypertensive rats and congestive heart failure rats. The contribution of vasoconstrictor intensities of basal renal sympathetic nerve activity to limiting renal blood flow variability may be important in the stabilization of glomerular filtration rate.

Influence of fluid resuscitation on renal microvascular PO2 in a normotensive rat model of endotoxemia

PubMed Central

Johannes, Tanja; Mik, Egbert G; Nohé, Boris; Raat, Nicolaas JH; Unertl, Klaus E; Ince, Can

2006-01-01

Introduction Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO2 (μPO2) and oxygen consumption (VO2,ren), that endotoxemia is associated with a diminished kidney function, that fluid resuscitation can restore μPO2, VO2,ren and kidney function, and that colloids are more effective than crystalloids. Methods Male Wistar rats received a one-hour intravenous infusion of lipopolysaccharide, followed by resuscitation with HES130/0.4 (Voluven®), HES200/0.5 (HES-STERIL® ® 6%) or Ringer's lactate. The renal μPO2 in the cortex and medulla and the renal venous PO2 were measured by a recently published phosphorescence lifetime technique. Results Endotoxemia induced a reduction in renal blood flow and anuria, while the renal μPO2 and VO2,ren remained relatively unchanged. Resuscitation restored renal blood flow, renal oxygen delivery and kidney function to baseline values, and was associated with oxygen redistribution showing different patterns for the different compounds used. HES200/0.5 and Ringer's lactate increased the VO2,ren, in contrast to HES130/0.4. Conclusion The loss of kidney function during endotoxemia could not be explained by an oxygen deficiency. Renal oxygen redistribution could for the first time be demonstrated during fluid resuscitation. HES130/0.4 had no influence on the VO2,ren and restored renal function with the least increase in the amount of renal work. PMID:16784545

AGXT2 rs37369 polymorphism predicts the renal function in patients with chronic heart failure.

PubMed

Hu, Xiao-Lei; Zeng, Wen-Jing; Li, Mu-Peng; Yang, Yong-Long; Kuang, Da-Bin; Li, He; Zhang, Yan-Jiao; Jiang, Chun; Peng, Li-Ming; Qi, Hong; Zhang, Ke; Chen, Xiao-Ping

2017-12-30

Patients with chronic heart failure (CHF) are often accompanied with varying degrees of renal diseases. The purpose of this study was to identify rs37369 polymorphism of AGXT2 specific to the renal function of CHF patients. A total of 1012 southern Chinese participants, including 487 CHF patients without history of renal diseases and 525 healthy volunteers, were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes of AGXT2 rs37369 polymorphism. Levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected to indicate the renal function of the participants. BUN level was significantly higher in CHF patients without history of renal diseases compared with healthy volunteers (p=0.000). And the similar result was also obtained for SCr (p=0.000). Besides, our results indicated that the level of BUN correlated significantly with SCr in both the CHF patients without renal diseases (r=0.4533, p<0.0001) and volunteers (r=0.2489, p<0.0001). Furthermore, we found that the AGXT2 rs37369 polymorphism could significantly affect the level of BUN in CHF patients without history of renal diseases (p=0.036, AA+AG vs GG). Patients with rs37369 GG genotype showed a significantly reduced level of BUN compared to those with the AA genotype (p=0.024), and the significant difference was still observed in the smokers of CHF patients without renal diseases (p=0.023). In conclusion, we found that CHF might induce the impairment of kidney and cause deterioration of renal function. AGXT2 rs37369 polymorphism might affect the renal function of CHF patients free from renal diseases, especially in patients with cigarette smoking. Copyright © 2017. Published by Elsevier B.V.

The prevalence and implications of BK virus replication in non-renal solid organ transplant recipients: A systematic review.

PubMed

Viswesh, Velliyur; Yost, Sarah E; Kaplan, Bruce

2015-07-01

The significance of BK viruria and viremia in non-renal solid organ transplants is poorly understood. A systematic review was performed reviewing the incidence and implications of BK virus replication in non-renal solid organ transplants. Ninety-seven studies were identified, of which 18 including lung, heart, liver and pancreas transplants were included. The overall incidence of BK viruria and viremia was 20% and 3% respectively and 17 cases of BK nephropathy were identified. Heart transplant recipients had a higher overall incidence of BK viremia than other non-renal organ types, and the majority of cases of BK virus-associated nephropathy were in heart transplant recipients. The incidence of BK viremia was significantly lower in non-renal solid organ transplants than that of renal transplant recipients and BK virus-associated nephropathy was rare. BK virus-associated nephropathy may be considered in heart transplant recipients who have unexplained and persistent renal dysfunction not attributable to other causes. Copyright © 2015 Elsevier Inc. All rights reserved.

Microcirculation of human pancreatic islets transplanted under the renal capsule of nude mice.

PubMed

Jansson, L; Tyrberg, B; Carlsson, P O; Nordin, A; Andersson, A; Källskog O

2001-08-27

The aim was to measure the capillary blood pressure in transplanted human islets. Human islets were isolated at the Central Unit of the beta-cell Transplant in Brussels, Belgium. After transport to our laboratory, the islets were implanted under the renal capsule of normoglycemic nude mice. Two weeks later the capillary and venous blood pressures in the islet graft and adjacent renal parenchyma were measured with a micropuncture technique. Capillary blood pressure was approximately 5-8 mmHg in both graft and renal capillaries: twice as high as in native islets. Venous blood pressures were similar (4-5 mmHg) in the veins draining the graft and in the renal interlobular veins. All veins leading from the graft emptied into the renal parenchyma, that is, into interlobular veins. The capillary hypertension seen in transplanted human islets is probably necessary to secure adequate drainage through the renal veins. Whether this contributes to the poor results of long-term islet graft survival is unknown.

A quantitative systems physiology model of renal function and blood pressure regulation: Model description.

PubMed

Hallow, K M; Gebremichael, Y

2017-06-01

Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses. Here we present a model of renal physiology and control mechanisms involved in maintaining sodium and water homeostasis. This model represents the core renal physiological processes involved in many research questions in drug development. The model runs in R and the code is made available. In a companion article, we present a case study using the model to explore mechanisms and pharmacology of salt-sensitive hypertension. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Repeated daclizumab administration to delay the introduction of calcineurin inhibitors in heart transplant patients with postoperative renal dysfunction.

PubMed

Sánchez Lázaro, Ignacio J; Almenar Bonet, Luis; Martínez Dolz, Luis; Buendía Fuentes, Francisco; Navarro Manchón, Josep; Agüero Ramón-Llin, Jaime; Vicente Sánchez, José Luis; Salvador Sanz, Antonio

2011-03-01

Daclizumab is an interleukin-2 receptor antagonist which is used for induction therapy in heart transplant patients. It has few side effects and is associated with a low infection rate. Postoperative renal failure after heart transplantation is common and potentially fatal. The administration of calcineurin inhibitors in the postoperative period can aggravate the situation. We report the cases of six patients who underwent heart transplantation and developed acute renal failure in the immediate postoperative period. All were administered daclizumab weekly to avoid the introduction of calcineurin inhibitors and to facilitate recovery of renal function. Calcineurin inhibitors were introduced only once renal function had improved. Renal function recovered in all cases and there was a low complication rate. The administration of repeated doses of daclizumab to patients who experience acute postoperative renal failure after heart transplantation may provide an alternative therapeutic approach that enables calcineurin inhibitors to be avoided and, consequently, renal function to recover. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

MRI to assess renal structure and function.

PubMed

Artunc, Ferruh; Rossi, Cristina; Boss, Andreas

2011-11-01

In addition to excellent anatomical depiction, MRI techniques have expanded to study functional aspects of renal physiology, such as renal perfusion, glomerular filtration rate (GFR) or tissue oxygenation. This review will focus on current developments with an emphasis on clinical applicability. The method of GFR determination is largely heterogeneous and still has weaknesses. However, the technique of employing liver disappearance curves has been shown to be accurate in healthy persons and patients with chronic kidney disease. In potential kidney donors, complete evaluation of kidney anatomy and function can be accomplished in a single-stop investigation. Techniques without contrast media can be utilized to measure renal tissue oxygenation (blood oxygen level-dependent MRI) or perfusion (arterial spin labeling) and could aid in the diagnosis and treatment of ischemic renal diseases, such as renal artery stenosis. Diffusion imaging techniques may provide information on spatially restricted water diffusion and tumor cellularity. Functional MRI opens new horizons in studying renal physiology and pathophysiology in vivo. Although extensively utilized in research, labor-intensive postprocessing and lack of standardization currently limit the clinical applicability of functional MRI. Further studies are necessary to evaluate the clinical value of functional magnetic resonance techniques for early discovery and characterization of kidney disease.

[Impaired renal function: be aware of exogenous factors].

PubMed

van der Meijden, Wilbert A G; Smak Gregoor, Peter J H

2013-01-01

Renal function is currently estimated using the Modification of Diet in Renal Disease (MDRD) formula, which is partly based on the serum creatinine level. Patients with impaired renal function are referred to nephrologists in accordance with the Dutch national transmural agreement for 'Chronic renal impairment'. A 54-year-old woman without significant history was referred to analyse a coincidentally found decline in the estimated glomerular filtration rate (eGFR). The patient had no complaints and used no medication except creatine supplements. Additional diagnostic testing showed no abnormalities. After cessation of creatine supplementation, the calculated renal function normalized. Serum creatinine is a reflection of muscle mass. The use of creatine-containing dietary supplements, such as creatine ethyl ester, can influence serum creatinine levels and therefore the eGFR as calculated with the MDRD formula. The use of supplements deserves attention when taking the history.

Worsening renal function defined as an absolute increase in serum creatinine is a biased metric for the study of cardio-renal interactions.

PubMed

Testani, Jeffrey M; McCauley, Brian D; Chen, Jennifer; Shumski, Michael; Shannon, Richard P

2010-01-01

Worsening renal function (WRF) during the treatment of decompensated heart failure, frequently defined as an absolute increase in serum creatinine >or=0.3 mg/dl, has been reported as a strong adverse prognostic factor in several studies. We hypothesized that this definition of WRF is biased by baseline renal function secondary to the exponential relationship between creatinine and renal function. We reviewed consecutive admissions with a discharge diagnosis of heart failure. An increase in creatinine >or=0.3 mg/dl (WRF(CREAT)) was compared to a decrease in GFR >or=20% (WRF(GFR)). Overall, 993 admissions met eligibility. WRF(CREAT) occurred in 31.5% and WRF(GFR) in 32.7%. WRF(CREAT) and WRF(GFR) had opposing relationships with baseline renal function (OR = 1.9 vs. OR = 0.51, respectively, p < 0.001). Both definitions had similar unadjusted associations with death at 30 days [WRF(GFR) OR = 2.3 (95% CI 1.1-4.8), p = 0.026; WRF(CREAT) OR = 2.1 (95% CI 1.0-4.4), p = 0.047]. Controlling for baseline renal insufficiency, WRF(GFR) added incrementally in the prediction of mortality (p = 0.009); however, WRF(CREAT) did not (p = 0.11). WRF, defined as an absolute change in serum creatinine, is heavily biased by baseline renal function. An alternative definition of WRF should be considered for future studies of cardio-renal interactions. Copyright 2010 S. Karger AG, Basel.

Renal subcapsular rim sign. Radionuclide pattern

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howman-Giles, R.; Gett, M.; Roy, P.

1986-04-01

The renal cortical rim sign is a radiological term describing the thin peripheral nephrogram of 2-4 mm thick which is from the peri-renal capsular collateral circulation in an otherwise nonfunctioning kidney. Radionuclides are used frequently in the estimation of renal function. A neonate with renal vein thrombosis demonstrated a rim sign on renal scan with Technetium DTPA. The rim sign on renal scan can be differentiated from severe hydronephrosis or multicystic kidney both of which may have a peripheral thin cortex which functions late on the renal scan. The rim sign in renal vein thrombosis was best visualized during themore » early blood pool phase when there was a considerable amount of radioactivity in the blood pool.« less

Impact of Impaired Renal Function on Gadolinium Retention After Administration of Gadolinium-Based Contrast Agents in a Mouse Model.

PubMed

Kartamihardja, A Adhipatria P; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito

2016-10-01

The aim of this study was to investigate the impact of impaired renal function on gadolinium (Gd) retention in various organs after Gd-based contrast agent injection. After local animal care and review committee approval, 23 normal mice and 26 with renal failure were divided into 4 treatment groups (Gd-DTPA-BMA, 5 mmol/kg; Gd-DOTA, 5 mmol/kg; GdCl3, 0.02 mmol/kg; and saline, 250 μL). Each agent was intravenously administered on weekdays for 4 weeks. Samples were collected on days 3 (short-term) and 45 (long-term) after the last injection. Gadolinium concentrations were quantified by inductively coupled plasma-mass spectrometry. Three mice with renal failure and 2 normal mice in the GdCl3 group and 1 mouse with renal failure in the Gd-DTPA-BMA group died. In the Gd-DTPA-BMA group, impaired renal function increased short-term Gd retention in the liver, bone, spleen, skin, and kidney (P < 0.01) but did not affect long-term Gd retention. Gd-DTPA-BMA showed higher Gd retention than Gd-DOTA. Although Gd retention in the Gd-DOTA group was generally low, impaired renal function increased only long-term hepatic Gd retention. Hepatic and splenic Gd retentions were significantly higher than other organs' Gd retention in the GdCl3 group (P < 0.01). Renal function did not affect brain Gd retention, regardless of the Gd compound used. The tendency of Gd retention varied according to the agent, regardless of renal function. Although renal impairment increased short-term Gd retention after Gd-DTPA-BMA administration, long-term Gd retention for Gd-based contrast agents was almost unaffected by renal function, suggesting that the chemical structures of retained Gd may not be consistent and some Gd is slowly eliminated after initially being retained.

Predictors of Renal Function Decline in Chinese Patients with Type 2 Diabetes Mellitus and in a Subgroup of Normoalbuminuria: A Retrospective Cohort Study.

PubMed

Hu, Ping; Zhou, Xiang-Hai; Wen, Xin; Ji, Linong

2016-10-01

Risk factors related to renal function decline in type 2 diabetes mellitus (T2DM) remain uncertain. This study aimed to investigate risk factors in relation to renal function decline in patients with T2DM and in a subgroup of patients with normoalbuminuria. This study was a retrospective cohort study, which included 451 patients with T2DM aged 63 ± 14 years admitted to a tertiary hospital in Beijing, China, between April and December 2010 and followed up for 6-60 months. Endpoint was renal function decline, defined as estimated glomerular filtration rate less than 60 mL/min 1.73 m 2 or at least twofold increase of serum creatinine. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) for candidate risk factors of renal function decline. After a median follow-up of 3.3 years, 94 (20.8%) patients developed renal function decline. Increased age (HR, 1.045; 95% CI, 1.020-1.070), albuminuria (HR, 1.956; 95%CI, 1.271-3.011), mild renal dysfunction (HR, 4.521; 95%CI, 2.734-7.476), hyperfiltration (HR, 3.897; 95%CI, 1.572-9.663), and increased hemoglobin A1c (HR, 1.128; 95%CI, 1.020-1.249) were identified as major risk factors. Among a subgroup of 344 patients with normoalbuminuria at baseline, 53 (15.4%) patients developed renal function decline. Increased age (HR, 1.089; 95%CI, 1.050-1.129), mild renal dysfunction (HR, 4.667; 95%CI, 2.391-9.107), hyperfiltration (HR, 5.677; 95%CI, 1.544-20.872), smoking (HR, 2.886; 95%CI, 1.370-6.082), higher pulse pressure (HR, 1.022; 95%CI, 1.004-1.040), and increased fasting glucose (HR, 1.104; 95%CI, 1.020-1.194) were major risk factors. Risk factors of diabetic renal impairment in T2DM should be screened and evaluated at an early stage of diabetes. Albuminuria, mild renal dysfunction, hyperfiltration, increased blood glucose, increased pulse pressure, and smoking were all predictors for diabetic renal impairment and interventions that focus on these risk factors may reduce further decline in renal function.

Vesicoureteral reflux in the primate IV: does reflux harm the kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, J.A.; Fischman, N.H.; Thomas, R.

1982-09-01

It has been said that vesicoureteral reflux causes renal scarring because of intrarenal reflux. We studied reflux in the monkey because of its similarity to man, especially in regard to the incidence of vesicoureteral reflux and chronic pyelonephritis. High pressure moderate grade reflux was produced and renal function followed by means of quantitative renal camera studies using /sup 131/I hippuran. There was no change in renal function from sterile reflux even when intrarenal reflux occurred. When, however, infection was introduced, renal function decreased. We concluded that sterile moderate vesicoureteral or intrarenal reflux does not harm the kidney.

Why and how to measure renal function in patients with liver disease.

PubMed

Piano, Salvatore; Romano, Antonietta; Di Pascoli, Marco; Angeli, Paolo

2017-01-01

Patients with advanced liver disease frequently have impaired renal function. Both acute kidney injury (AKI) and chronic kidney disease (CKD) are quite common in patients with cirrhosis and both are associated with a worse prognosis in these patients. A careful assessment of renal function is highly important in these patients to help physicians determine their diagnosis, prognosis and therapeutic management and to define transplantation strategies (liver transplantation alone vs simultaneous liver and kidney transplantation). Although they are still widely used in clinical practice, conventional biomarkers of renal function such as serum creatinine have several limitations in these patients. Recent progress has been made in the evaluation of renal function and new diagnostic criteria for AKI have been proposed. However, certain issues such as the noninvasive assessment of the glomerular filtration rate and/or improvement in the differential diagnosis between hepatorenal syndrome and acute tubular necrosis must still be addressed. The purposes of this paper are: (i) to highlight the importance of the evaluation of renal function in patients with cirrhosis; (ii) to review the state of the art in the assessment of renal function in these patients as well as advances that we expect will be made to improve the accuracy of available tools. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cigarette smoking causes epigenetic changes associated with cardiorenal fibrosis

PubMed Central

Haller, Steven T.; Fan, Xiaoming; Xie, Jeffrey X.; Kennedy, David J.; Liu, Jiang; Yan, Yanling; Hernandez, Dawn-Alita; Mathew, Denzil P.; Cooper, Christopher J.; Shapiro, Joseph I.; Tian, Jiang

2016-01-01

Clinical studies indicate that smoking combustible cigarettes promotes progression of renal and cardiac injury, leading to functional decline in the setting of chronic kidney disease (CKD). However, basic studies using in vivo small animal models that mimic clinical pathology of CKD are lacking. To address this issue, we evaluated renal and cardiac injury progression and functional changes induced by 4 wk of daily combustible cigarette smoke exposure in the 5/6th partial nephrectomy (PNx) CKD model. Molecular evaluations revealed that cigarette smoke significantly (P < 0.05) decreased renal and cardiac expression of the antifibrotic microRNA miR-29b-3 and increased expression of molecular fibrosis markers. In terms of cardiac and renal organ structure and function, exposure to cigarette smoke led to significantly increased systolic blood pressure, cardiac hypertrophy, cardiac and renal fibrosis, and decreased renal function. These data indicate that decreased expression of miR-29b-3p is a novel mechanism wherein cigarette smoke promotes accelerated cardiac and renal tissue injury in CKD. (155 words) PMID:27789733

Dosing of cytotoxic chemotherapy: impact of renal function estimates on dose.

PubMed

Dooley, M J; Poole, S G; Rischin, D

2013-11-01

Oncology clinicians are now routinely provided with an estimated glomerular filtration rate on pathology reports whenever serum creatinine is requested. The utility of using this for the dose determination of renally excreted drugs compared with other existing methods is needed to inform practice. Renal function was determined by [Tc(99m)]DTPA clearance in adult patients presenting for chemotherapy. Renal function was calculated using the 4-variable Modification of Diet in Renal Disease (4v-MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockcroft and Gault (CG), Wright and Martin formulae. Doses for renal excreted cytotoxic drugs, including carboplatin, were calculated. The concordance of the renal function estimates according to the CKD classification with measured Tc(99m)DPTA clearance in 455 adults (median age 64.0 years: range 17-87 years) for the 4v-MDRD, CKD-EPI, CG, Martin and Wright formulae was 47.7%, 56.3%, 46.2%, 56.5% and 60.2%, respectively. Concordance for chemotherapy dose for these formulae was 89.0%, 89.5%, 85.1%, 89.9% and 89.9%, respectively. Concordance for carboplatin dose specifically was 66.4%, 71.4%, 64.0%, 73.8% and 73.2%. All bedside formulae provide similar levels of concordance in dosage selection for the renal excreted chemotherapy drugs when compared with the use of a direct measure of renal function.

Nephrogenous Cyclic Adenosine Monophosphate as a Parathyroid Function Test

PubMed Central

Broadus, Arthur E.; Mahaffey, Jane E.; Bartter, Frederic C.; Neer, Robert M.

1977-01-01

Nephrogenous cyclic AMP (NcAMP), total cyclic AMP excretion (UcAMP), and plasma immunoreactive parathyroid hormone (iPTH), determined with a multivalent antiserum, were prospectively measured in 55 control subjects, 57 patients with primary hyperparathyroidism (1°HPT), and 10 patients with chronic hypoparathyroidism. In the group with 1° HPT, NcAMP was elevated in 52 patients (91%), and similar elevations were noted in subgroups of 26 patients with mild (serum calcium ≤10.7 mg/dl) or intermittent hypercalcemia, 19 patients with mild renal insufficiency (mean glomerular filtration rate, 64 ml/min), and 10 patients with moderate renal insufficiency (mean glomerular filtration rate, 43 ml/min). Plasma iPTH was increased in 41 patients (73%). The development of a parametric expression for UcAMP was found to be critically important in the clinical interpretation of results for total cAMP excretion. Because of renal impairment in a large number of patients, the absolute excretion rate of cAMP correlated poorly with the hyperparathyroid state. Expressed as a function of creatinine excretion, UcAMP was elevated in 81% of patients with 1° HPT, but the nonparametric nature of the expression led to a number of interpretive difficulties. The expression of cAMP excretion as a function of glomerular filtration rate was developed on the basis of the unique features of cAMP clearance in man, and this expression, which provided elevated values in 51 (89%) of the patients with 1° HPT, avoided entirely the inadequacies of alternative expressions. Results for NcAMP and UcAMP in nonazotemic and azotemic patients with hypoparathyroidism confirmed the validity of the measurements and the expressions employed. PMID:197123

Proposal for a functional classification system of heart failure in patients with end-stage renal disease: proceedings of the acute dialysis quality initiative (ADQI) XI workgroup.

PubMed

Chawla, Lakhmir S; Herzog, Charles A; Costanzo, Maria Rosa; Tumlin, James; Kellum, John A; McCullough, Peter A; Ronco, Claudio

2014-04-08

Structural heart disease is highly prevalent in patients with chronic kidney disease requiring dialysis. More than 80% of patients with end-stage renal disease (ESRD) are reported to have cardiovascular disease. This observation has enormous clinical relevance because the leading causes of death for patients with ESRD are of cardiovascular disease etiology, including heart failure, myocardial infarction, and sudden cardiac death. The 2 systems most commonly used to classify the severity of heart failure are the New York Heart Association (NYHA) functional classification and the American Heart Association (AHA)/American College of Cardiology (ACC) staging system. With rare exceptions, patients with ESRD who do not receive renal replacement therapy (RRT) develop signs and symptoms of heart failure, including dyspnea and edema due to inability of the severely diseased kidneys to excrete sodium and water. Thus, by definition, nearly all patients with ESRD develop a symptomatology consistent with heart failure if fluid removal by RRT is delayed. Neither the AHA/ACC heart failure staging nor the NYHA functional classification system identifies the variable symptomatology that patients with ESRD experience depending upon whether evaluation occurs before or after fluid removal by RRT. Consequently, the incidence, severity, and outcomes of heart failure in patients with ESRD are poorly characterized. The 11th Acute Dialysis Quality Initiative has identified this issue as a critical unmet need for the proper evaluation and treatment of heart failure in patients with ESRD. We propose a classification schema based on patient-reported dyspnea assessed both pre- and post-ultrafiltration, in conjunction with echocardiography. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Dietary Sodium Modulation of Aldosterone Activation and Renal Function During the Progression of Experimental Heart Failure Miller: Dietary Sodium and Early Heart Failure

PubMed Central

Miller, Wayne L.; Borgeson, Daniel D.; Grantham, J. Aaron; Luchner, Andreas; Redfield, Margaret M.; Burnett, John C.

2015-01-01

Aims Aldosterone activation is central to the sodium-fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Methods and Results Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: 1) high sodium [250 mEq (5.8 grams) per day, n=6]; 2) standard sodium [58 mEq (1.3 grams) per day, n=6]; and 3) sodium restriction [11 mEq (0.25 grams) per day, n=6]. During the 38 day study hemodynamics, renal function, renin activity (PRA), and aldosterone were measured. Changes in hemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups, however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Conclusions Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression. PMID:25823360

Frequency response of the renal vasculature in congestive heart failure.

PubMed

DiBona, Gerald F; Sawin, Linda L

2003-04-29

The renal vasoconstrictor response to renal nerve stimulation is greater in congestive heart failure (CHF) rats than in control rats. This study tested the hypothesis that the enhanced renal vasoconstrictor response to renal nerve stimulation in CHF is a result of an impairment in the low-pass filter function of the renal vasculature. In response to conventional graded-frequency renal nerve stimulation, the reductions in renal blood flow at each stimulation frequency were greater in CHF rats than control rats. A pseudorandom binary sequence pattern of renal nerve stimulation was used to examine the frequency response of the renal vasculature. Although this did not affect the renal blood flow power spectrum in control rats, there was a 10-fold increase in renal blood flow power over the frequency range of 0.01 to 1.0 Hz in CHF rats. On analysis of transfer function gain, attenuation of the renal nerve stimulation input signal was similar in control and CHF rats over the frequency range of 0.001 to 0.1 Hz. However, over the frequency range of 0.1 to 1.0 Hz, although there was progressive attenuation of the input signal (-30 to -70 dB) in control rats, CHF rats exhibited a flat gain response (-20 dB) without progressive attenuation. The enhanced renal vasoconstrictor response to renal nerve stimulation in CHF rats is caused by an alteration in the low-pass filter function of the renal vasculature, resulting in a greater transfer of input signals into renal blood flow in the 0.1 to 1.0 Hz range.

Clinical outcome of patients with heart failure and preserved left ventricular function.

PubMed

Gotsman, Israel; Zwas, Donna; Planer, David; Azaz-Livshits, Tanya; Admon, Dan; Lotan, Chaim; Keren, Andre

2008-11-01

Patients with heart failure have a poor prognosis. However, it has been presumed that patients with heart failure and preserved left ventricular function (LVF) may have a more benign prognosis. We evaluated the clinical outcome of patients with heart failure and preserved LVF compared with patients with reduced function and the factors affecting prognosis. We prospectively evaluated 289 consecutive patients hospitalized with a definite clinical diagnosis of heart failure based on typical symptoms and signs. They were divided into 2 subsets based on echocardiographic LVF. Patients were followed clinically for a period of 1 year. Echocardiography showed that more than one third (36%) of the patients had preserved systolic LVF. These patients were more likely to be older and female and have less ischemic heart disease. The survival at 1 year in this group was poor and not significantly different from patients with reduced LVF (75% vs 71%, respectively). The adjusted survival by Cox regression analysis was not significantly different (P=.25). However, patients with preserved LVF had fewer rehospitalizations for heart failure (25% vs 35%, P<.05). Predictors of mortality in the whole group by multivariate analysis were age, diabetes, chronic renal failure, atrial fibrillation, residence in a nursing home, and serum sodium < or = 135 mEq/L. The prognosis of patients with clinical heart failure with or without preserved LVF is poor. Better treatment modalities are needed in both subsets.

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban.

PubMed

Chang, Ming; Yu, Zhigang; Shenker, Andrew; Wang, Jessie; Pursley, Janice; Byon, Wonkyung; Boyd, Rebecca A; LaCreta, Frank; Frost, Charles E

2016-05-01

This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr ) as a measure of renal function. The relationships between 24-hour CLcr and iohexol clearance, estimated CLcr (Cockcroft-Gault equation), and estimated glomerular filtration rate (modification of diet in renal disease [MDRD] equation) were also assessed. Secondary objectives included assessment of safety and tolerability as well as international normalized ratio (INR) and anti-factor Xa activity as pharmacodynamic endpoints. The regression analysis showed that decreasing renal function resulted in modestly increased apixaban exposure (AUC∞ increased by 44% in severe impairment with a 24-hour CLcr of 15 mL/min, compared with subjects with normal renal function), but it did not affect Cmax or the direct relationship between apixaban plasma concentration and anti-factor Xa activity or INR. The assessment of renal function measured by iohexol clearance, Cockcroft-Gault, and MDRD was consistent with that determined by 24-hour CLcr . Apixaban was well tolerated in this study. These results suggest that dose adjustment of apixaban is not required on the basis of renal function alone. © 2015, The American College of Clinical Pharmacology.

Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

PubMed

Minhas, Anum S; Jiang, Qingmei; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2016-11-01

All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance <50 mL/min and 23 (12.2 %) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

Short and long-term effects of continuous versus intermittent loop diuretics treatment in acute heart failure with renal dysfunction.

PubMed

Palazzuoli, Alberto; Pellegrini, Marco; Franci, Beatrice; Beltrami, Matteo; Ruocco, Gaetano; Gonnelli, Stefano; Angelini, Gianni D; Nuti, Ranuccio

2015-02-01

Intravenous loop diuretics are still the cornerstone of therapy in acute decompensated heart failure, however, the optimal dosage and administration strategies remain poorly defined particularly in patients with an associated renal dysfunction. This is a single-center, pilot, randomized trial involving patients with acute HF and renal dysfunction. Patients were assigned to receive continuous furosemide infusion (cIV) or bolus injections of furosemide (iIV). Primary end points were the evaluation of urine output volumes, renal function, and b-type natriuretic peptide (BNP) levels during treatment time. Secondary end point included: weight loss, length of hospitalization, differences in plasma electrolytes, need for additional treatment, and evaluation of cardiac events during follow-up period. 57 patients were included in the study. The cIV group showed an increase in urine output (2,505 ± 796 vs 2140 ± 468 ml/day, p < 0.04) and a more significant decrease of BNP levels in respect to the iIV group (679.6 ± 397 vs 949 ± 548 pg/ml, p < 0.04). We observed a significant increase in creatinine levels (1.78 ± 0.5 vs 1.41 ± 0.3 mg/dl, p < 0.01), and a reduction of the estimated glomerular filtration rate in cIV (44.8 ± 6.1 vs 46.7 ± 6.1 ml/min, p < 0.05). We observed a significant difference in eGFR (p = 0.01), creatinine (p = 0.02) and BNP levels (p = 0.03) from baseline to the end of treatment in both groups. A significant increase of in-hospital additional treatment as well as length of hospitalization was observed in cIV. Finally, cIV revealed a higher rate of adverse events during the follow-up period (p < 0.03). cIV appears to provide a more efficient diuresis and BNP level reduction during hospitalization, however, it was associated with increased rate of worsening renal function during hospitalization. cIV also appears related to a longer hospitalization and an increased number of adverse events during follow-up. For all of these reasons, a larger multi-center study is required to determine whether high-dose diuretics are responsible for worsening renal function and to define the best modality of administration.

Magnetic Resonance Imaging-Derived Renal Oxygenation and Perfusion During Continuous, Steady-State Angiotensin-II Infusion in Healthy Humans.

PubMed

van der Bel, René; Coolen, Bram F; Nederveen, Aart J; Potters, Wouter V; Verberne, Hein J; Vogt, Liffert; Stroes, Erik S G; Krediet, C T Paul

2016-03-28

The role of kidney hypoxia is considered pivotal in the progression of chronic kidney disease. A widely used method to assess kidney oxygenation is blood oxygen level dependent (BOLD)-magnetic resonance imaging (MRI), but its interpretation remains problematic. The BOLD-MRI signal is the result of kidney oxygen consumption (a proxy of glomerular filtration) and supply (ie, glomerular perfusion). Therefore, we hypothesized that with pharmacological modulation of kidney blood flow, renal oxygenation, as assessed by BOLD-MRI, correlates to filtration fraction (ie, glomerular filtration rate/effective renal plasma flow) in healthy humans. Eight healthy volunteers were subjected to continuous angiotensin-II infusion at 0.3, 0.9, and 3.0 ng/kg per minute. At each dose, renal oxygenation and blood flow were assessed using BOLD and phase-contrast MRI. Subsequently, "gold standard" glomerular filtration rate/effective renal plasma flow measurements were performed under the same conditions. Renal plasma flow decreased dose dependently from 660±146 to 467±103 mL/min per 1.73 m(2) (F[3, 21]=33.3, P<0.001). Glomerular filtration rate decreased from 121±23 to 110±18 mL/min per 1.73 m(2) (F[1.8, 2.4]=6.4, P=0.013). Cortical transverse relaxation rate (R2*; increases in R2* represent decreases in oxygenation) increased by 7.2±3.8% (F[3, 21]=7.37, P=0.001); medullar R2* did not change. Cortical R2* related to filtration fraction (R(2) 0.46, P<0.001). By direct comparison between "gold standard" kidney function measurements and BOLD MRI, we showed that cortical oxygenation measured by BOLD MRI relates poorly to glomerular filtration rate but is associated with filtration fraction. For future studies, there may be a need to include renal plasma flow measurements when employing renal BOLD-MRI. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dubovsky, E.V.; Curtis, J.J.; Luke, R.G.

Impaired function of renal allografts caused by recurrent disease or rejection is often accompanied by hypertension. The etiology of persistent severe hypertension in recipients with good renal function is more difficult to explain. To study this problem, 33 patients with mean arterial pressure (MAP) > 105 mm Hg (at least one year after transplantation) were tested. When compared to a normotensive group, they were found to have increased renal vascular resistance, lower ERPF, and increased renin-angiotensin activity. The effect of Captopril, a converting enzyme inhibitor, was studied to evaluate the role of angiotension. The paper concludes that Captopril test maymore » permit differentiation between native kidney-dependent hypertension (increase in ERPF) and functionally active renal artery stenosis (decline in ERPF) in patients with persistent hypertension and good renal function.« less

Reference values of renal tubular function tests are dependent on age and kidney function.

PubMed

Bech, Anneke P; Wetzels, Jack F M; Nijenhuis, Tom

2017-12-01

Electrolyte disorders due to tubular disorders are rare, and knowledge about validated clinical diagnostic tools such as tubular function tests is sparse. Reference values for tubular function tests are based on studies with small sample size in young healthy volunteers. Patients with tubular disorders, however, frequently are older and can have a compromised renal function. We therefore evaluated four tubular function tests in individuals with different ages and renal function. We performed furosemide, thiazide, furosemide-fludrocortisone, and desmopressin tests in healthy individuals aged 18-50 years, healthy individuals aged more than 50 years and individuals with compromised renal function. For each tubular function test we included 10 individuals per group. The responses in young healthy individuals were in line with previously reported values in literature. The maximal increase in fractional chloride excretion after furosemide was below the lower limit of young healthy individuals in 5/10 older subjects and in 2/10 patients with compromised renal function. The maximal increase in fractional chloride excretion after thiazide was below the lower limit of young healthy individuals in 6/10 older subjects and in 7/10 patients with compromised renal function. Median maximal urine osmolality after desmopressin was 1002 mosmol/kg H 2 O in young healthy individuals, 820 mosmol/kg H 2 O in older subjects and 624 mosmol/kg H 2 O in patients with compromised renal function. Reference values for tubular function tests obtained in young healthy adults thus cannot simply be extrapolated to older patients or patients with compromised kidney function. Larger validation studies are needed to define true reference values in these patient categories. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

PAROTID FLUID TOTAL PROTEIN IN PATIENTS WITH UREMIA AND PROTEINURIA.

DTIC Science & Technology

Stimulated parotid fluid samples (238) were collected from 32 patients to determine if altered renal function was associated with deviations in...tubular necrosis, and 15 had normal renal function. There were no significant differences in parotid fluid protein concentration or minute secretion associated with the state of renal function. (Author)

Acute and cumulative effects of carboplatin on renal function.

PubMed Central

Sleijfer, D. T.; Smit, E. F.; Meijer, S.; Mulder, N. H.; Postmus, P. E.

1989-01-01

Carboplatin, a cisplatinum analogue, has no reported nephrotoxicity in phase I/II studies, assessed by creatinine clearance. We prospectively determined renal function in 10 untreated lung cancer patients with normal baseline renal function, treated with carboplatin 400 mg m-2 day 1 and vincristine 2 mg day 1 and 8 every 4 weeks (max. five cycles) by means of clearance studies with 125I-sodium thalamate and 131I-hippurate to determine GFR and ERPF respectively. Tubular damage was monitored by excretion of tubular enzymes and relative beta 2-microglobulin clearance. During the first course no changes in renal function were seen. After the second course a significant fall in GFR and ERPF started, ultimately leading to a median decrease in GFR of 19.0% (range 6.8-38.7%) and in ERPF of 14% (range 0-38.9%). No increases in the excretion of tubular enzymes or changes in the relative beta 2-microglobulin clearances were seen. We conclude from our data that carboplatin causes considerable loss of renal function. Monitoring renal function in patients treated with multiple courses of carboplatin is warranted. PMID:2679841

Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT.

PubMed

Jackson, Price; Foroudi, Farshad; Pham, Daniel; Hofman, Michael S; Hardcastle, Nicholas; Callahan, Jason; Kron, Tomas; Siva, Shankar

2014-11-26

Stereotactic ablative body radiotherapy (SABR) has been proposed as a definitive treatment for patients with inoperable primary renal cell carcinoma. However, there is little documentation detailing the radiobiological effects of hypofractionated radiation on healthy renal tissue. In this study we describe a methodology for assessment of regional change in renal function in response to single fraction SABR of 26 Gy. In a patient with a solitary kidney, detailed follow-up of kidney function post-treatment was determined through 3-dimensional SPECT/CT imaging and (51)Cr-EDTA measurements. Based on measurements of glomerular filtration rate, renal function declined rapidly by 34% at 3 months, plateaued at 43% loss at 12 months, with minimal further decrease to 49% of baseline by 18 months. The pattern of renal functional change in (99m)Tc-DMSA uptake on SPECT/CT imaging correlates with dose delivered. This study demonstrates a dose effect relationship of SABR with loss of kidney function.

[Fetal urology].

PubMed

Jakobovits, Akos; Jakobovits, Antal

2009-06-14

Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

Neural control of renal function: role of renal alpha adrenoceptors.

PubMed

DiBona, G F

1985-01-01

Adrenoceptors of various subtypes mediate the renal functional responses to alterations in efferent renal sympathetic nerve activity, the neural component, and renal arterial plasma catecholamine concentrations, the humoral component, of the sympathoadrenergic nervous system. Under normal physiologic as well as hypertensive conditions, the influence of the renal sympathetic nerves predominates over that of circulating plasma catecholamines. In most mammalian species, increases in efferent renal sympathetic nerve activity elicit renal vasoconstrictor responses mediated predominantly by renal vascular alpha-1 adrenoceptors, increases in renin release mediated largely by renal juxtaglomerular granular cell beta-1 adrenoceptors with involvement of renal vascular alpha-1 adrenoceptors only when renal vasoconstriction occurs, and direct increases in renal tubular sodium and water reabsorption mediated predominantly by renal tubular alpha-1 adrenoceptors. In most mammalian species, alpha-2 adrenoceptors do not play a significant role in the renal vascular or renin release responses to renal sympathoadrenergic stimulation. Although renal tubular alpha-2 adrenoceptors do not mediate the increases in renal tubular sodium and water reabsorption produced by increases in efferent renal sympathetic nerve activity, they may be involved through their inhibitory effect on adenylate cyclase in modulating the response to other hormonal agents that influence renal tubular sodium and water reabsorption via stimulation of adenylate cyclase.

Longer time spent in bed attempting to sleep is associated with rapid renal function decline: the Dongfeng-Tongji cohort study.

PubMed

Li, Yizhun; Yang, Liangle; Wang, Hao; Jiang, Haijing; Qiu, Gaokun; Liu, Yiyi; Xiao, Yang; Yang, Handong; Wu, Tangchun; Zhang, Xiaomin

2018-03-01

Prospective evidence on the relation between time in bed and renal dysfunction remains limited. We aimed to investigate the association of time spent in bed attempting to sleep (TSBS) with renal function decline in a middle-aged and elderly Chinese population. About 16,733 eligible participants with a mean age of 62.3 years at baseline were included. Rapid renal function decline was defined as (baseline eGFR - revisit eGFR)/years of follow-up ≥5 mL/min per 1.73 m 2 /year. A total of 1738 study participants experienced rapid renal function decline after a median 4.6-year follow-up. Logistic regression models were used for multivariate analyses. The adjusted odds ratio (OR) of rapid renal function decline was 1.18 (95% CI: 1.02, 1.37) for TSBS ≥9 h/night compared with TSBS 7 to <8 h/night. This association remained significant (OR = 1.19, 95% CI: 1.03, 1.38) after further adjustment for sleep quality, midday napping and usage of sleeping pills. Particularly, the association appeared to be prominent in individuals with diabetes. Longer TSBS (≥9 h) was independently associated with an increased risk of rapid renal function decline. Our findings emphasized the importance to have optimal TSBS. Key messages Our study firstly investigated the association between time spent in bed attempting to sleep (TSBS) and renal dysfunction in Chinese adults. Compared with individuals TSBS 7 to <8 h, individuals with TSBS ≥9 h had 19% increased risk for rapid renal function decline after adjustment for multivariate confounders. The association appeared to be prominent in individuals with diabetes.

Enhanced renal prostaglandin production in the dog. I. Effects on renal function.

PubMed

Tannenbaum, J; Splawinski, J A; Oates, J A; Nies, A S

1975-01-01

The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 and F2alpha.PGE2given at 0.01-0.3 mug/kg min--1 produced dose-related increases in urine flow, sodium and potassium excretion, free water clearance, and renal blood flow. The glomerular filtration rage increased only at the lowest dose and the calculated filtration fraction fell. Arachidonic acid at 1.0-30.0 mug/kg min--1 similarly produced dose-related increases in electrolyte excretion, but the increase in renal blood flow was much less than that produced by PGE2 and there were no changes in glomerular filtration rate, filtration fraction, or free water clearances. PGF2alpha had essentially no effects at infusion rates of 0.03-1.0 mug/kg min--1. All renal effects of arachidonic acid were inhibited by simultaneous infusions of an inhibitor of prostaglandin synthetase, 5, 8, 11,14-eicosatetraynoic acid (20:4). None of the effects produced by PGE2 were inhibited by 20:4. These results indicate that enhanced endogenous renal prostaglandin synthesis, which can be produced by arachidonate infusion, results in significant alterations of renal function. This finding strengthens the hypothesis that renal prostaglandins formed in vivo have physiological importance as regulators of renal function.

A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

PubMed

Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

2018-06-01

Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

Safety and efficacy of repaglinide in type 2 diabetic patients with and without impaired renal function.

PubMed

Hasslacher, Christoph

2003-03-01

To evaluate the influence of renal impairment on the safety and efficacy of repaglinide in type 2 diabetic patients. This multinational, open-label study comprised a 6-week run-in period, continuing prestudy antidiabetic medication, followed by a titration period (1-4 weeks) and a 3-month maintenance period. Patients with normal renal function (n = 151) and various degrees of renal impairment (n = 130) were treated with repaglinide (maximal dose of 4 mg, three times daily). Safety and efficacy assessments were performed at baseline (end of run-in) and at the end of study treatment. The type and severity of adverse events during repaglinide treatment were similar to the run-in period. The number of patients with adverse events was not significantly related to renal function during run-in or repaglinide treatment. Percentage of patients with hypoglycemic episodes increased significantly (P = 0.007) with increasing severity of renal impairment during run-in but not during repaglinide treatment (P = 0.074). Metabolic control (HbA(1c) and fasting blood glucose) with repaglinide was unchanged from that on previous antidiabetic medication. Final repaglinide dose tended to be lower for patients with severe and extreme renal impairment than for patients with less severe renal impairment or normal renal function (P = 0.032). Repaglinide has a good safety and efficacy profile in type 2 diabetic patients complicated by renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal impairment.

Early impact of robot-assisted partial nephrectomy on renal function as assessed by renal scintigraphy.

PubMed

Luciani, Lorenzo G; Chiodini, Stefano; Donner, Davide; Cai, Tommaso; Vattovani, Valentino; Tiscione, Daniele; Giusti, Guido; Proietti, Silvia; Chierichetti, Franca; Malossini, Gianni

2016-06-01

To measure the early impact of robot-assisted partial nephrectomy (RAPN) on renal function as assessed by renal scan (Tc 99m-DTPA), addressing the issue of risk factors for ischemic damage to the kidney. All patients undergoing RAPN for cT1 renal masses between June 2013 and May 2014 were included in this prospective study. Renal function as expressed by glomerular filtration rate (GFR) was assessed by Technetium 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scan preoperatively and postoperatively at 1 month in every patient. A multivariable analysis was used for the determination of independent factors predictive of GFR decrease of the operated kidney. Overall, 32 patients underwent RAPN in the time interval. Median tumor size, blood loss, and ischemia time were 4 cm, 200 mL, and 24 min, respectively. Two grade III complications occurred (postoperative bleeding in the renal fossa, urinoma). The GFR of the operated kidney decreased significantly from 51.7 ± 15.1 mL/min per 1.73 m(2) preoperatively to 40, 12 ± 12.4 mL/min per 1.73 m(2) 1 month postoperatively (p = 0.001) with a decrease of 22.4 %. On multivariable analysis, only tumor size (p = 0.05) was a predictor of GFR decrease of the operated kidney. Robotic-assisted partial nephrectomy had a detectable impact on early renal function in a series of relatively large tumors and prevailing intermediate nephrometric risk. A mean decrease of 22 % of GFR as assessed by renal scan in the operated kidney was found at 1 month postoperatively. In multivariable analysis, tumor size only was a significant predictor of renal function loss.

Mucormycosis (zygomycosis) of renal allograft

PubMed Central

Gupta, Krishan L.; Joshi, Kusum; Kohli, Harbir S.; Jha, Vivekanand; Sakhuja, Vinay

2012-01-01

Fungal infection is relatively common among renal transplant recipients from developing countries. Mucormycosis, also known as zygomycosis, is one of the most serious fungal infections in these patients. The most common of presentation is rhino-cerebral. Isolated involvement of a renal allograft is very rare. A thorough search of literature and our medical records yielded a total of 24 cases with mucormycosis of the transplanted kidney. There was an association with cytomegalovirus (CMV) infection and anti-rejection treatment in these patients and most of these transplants were performed in the developing countries from unrelated donors. The outcome was very poor with an early mortality in 13 (54.5%) patients. Renal allograft mucormycosis is a relatively rare and potentially fatal complication following renal transplantation. Early diagnosis, graft nephrectomy and appropriate antifungal therapy may result in an improved prognosis for these patients. PMID:26069793

Long-term Effects of Off-Pump Coronary Bypass Versus Conventional Coronary Bypass Grafting on Renal Function.

PubMed

Hynes, Conor F; Colo, Sanchez; Amdur, Richard L; Chawla, Lakhmir S; Greenberg, Michael D; Trachiotis, Gregory D

2016-01-01

This study aimed to evaluate the short- and long-term effects of conventional on-pump coronary bypass grafting (cCABG) compared with off-pump coronary artery bypass (OPCAB) on renal function. A retrospective review of patients undergoing coronary bypass grafting from 2004 through 2013 at a single center was conducted. Preoperative renal function, perioperative acute kidney injury, and long-term glomerular filtration were evaluated. Multivariable analyses were used to determine factors contributing to short- and long-term renal impairment. A total of 234 patients underwent cCABG, and 582 underwent OPCAB. Patients undergoing OPCAB were significantly older, had greater preoperative renal dysfunction, had greater functional dependence, and took more hypertension medications. Multivariable analyses found that 30-day acute kidney injury was an independent risk factor for a 10% decline in glomerular filtration rate at 1 and 5 years (P < 0.0001 and 0.002, respectively). However, the use of cardiopulmonary bypass was not found to influence long-term renal function (P = 0.78 at 1 year, P = 0.76 at 5 years). The percentage of patients experiencing a 10% drop in renal function from baseline at 1 year (33% OPCAB, 35% cCABG; P = 0.73) and 5 years (16% OPCAB, 16% cCABG; P = 0.93) were not significantly different. Independent predictors of acute kidney injury included baseline kidney function (P = 0.04) and age (P < 0.0001), whereas cardiopulmonary bypass did not affect the incidence (P = 0.17). A propensity-matched analysis confirmed these findings. Acute kidney injury is a risk factor for long-term renal dysfunction after either bypass method and was not greater after cCABG compared with OPCAB. Patients undergoing OPCAB did not experience greater decrease in long-term kidney function despite having worse baseline kidney function.

Twelve shifting paradigms in diabetic renal disease and hypertension.

PubMed

Mogensen, Carl Erik

2008-11-13

In the last 30 years we have seen considerable progress in the management of patients with diabetes, in particular with diabetic renal disease. A number of paradigms have been broken down, namely the following, as a consequence, clinical care has improved dramatically. . Significant renal involvement and albuminuria is rare in patients with essential hypertension. 2. High GFR is good for prognosis. 3. Only proteinuric diabetic patients have a poor prognosis. 4. Microalbuminuria only predicts renal disease. 5. Reducing blood pressure may cause low perfusion in the kidney and other organs with long-term negative effect, especially on the glomerular filtration rate. 6. Only in the presence of high blood pressure, should microalbuminuric patients receive anti-hypertensive treatment, including blockade of the RAS. 7. Only reducing blood pressure by blocking RAS in diabetes is relevant and justified. 8. Normoalbuminuria as indicated in the present definition is 'normal'. 9. ACE-I or ARB can only be used separately. 10. Diastolic blood pressure and later systolic pulse pressure are the best parameters for blood pressure recording. 11. Microalbuminuria is the strongest risk marker in patients with type 1 diabetes. 12. Screening for microalbuminuria is relevant, but follow-up was not proposed (also regarding microalbuminuria). In the present situation, it is well-known that patients with essential hypertension may sometimes have microalbuminuria, and it is known that it predicts a poor prognosis. Interestingly, in type 1 diabetes, hyperfiltration is a marker for poor prognosis related to metabolic control. Thus hyperfiltration is a marker for bad development, but microalbuminuria (below the proteinuric level) is also associated with a poor prognosis. It was originally believed that microalbuminuria only predicts renal disease. However, surprisingly it predicts as well cardiovascular disease and early mortality. The story about blood pressure and progression of renal disease is interesting, because it was earlier believed that a certain high blood pressure was mandatory for preservation of the renal function. This appeared to be a completely wrong concept. The data regarding microalbuminuria suggest that patients with microalbuminuria should receive anti-hypertensive treatment, even patients with so-called normal blood pressure. This was confirmed in several trials and also included in the guidelines. Reducing blood pressure is important, but it appeared to be especially beneficial to block the renin-angiontensin system, and it is clear that albuminuria is a continuous variable and is also a risk factor. Earlier it was suggested to use ACE-inhibitors or ARBs. Now it is clear that it is possible to use a combination, with good theoretical background. In the history of hypertension, it was earlier believed that diastolic blood pressure was most important, but later on it was generally accepted that systolic is a better predictor and the goal for treatment and pulse pressure may be even better. Not only is microalbuminuria an important risk marker, but it is as well clear that regression of microalbuminuria is a good marker for a better prognosis in patients. Microalbuminuria is believed to be the strongest risk factor, but new studies actually suggest that a simple parameter such as self-rated health is crucial along with other factors. Regarding new developments, it is clear that new studies have led to several advancements in management in patients, for instance the Steno II study shows positive effect on mortality by multifactorial intervention. Similarly, the ADVANCE study also showed positive effect on mortality by more intensified anti-hypertensive treatment with an ACE-inhibitor. We are eagerly awaiting the results from glucose arm in the ADVANCE study, especially in the light of the ACCORD study showing increased mortality with too strict glycemic control with a goal of 6% in HbA1c.

Microvascular disease precedes the decline in renal function in the streptozotocin-induced diabetic rat

PubMed Central

Maric-Bilkan, Christine; Flynn, Elizabeth R.

2012-01-01

Diabetic nephropathy is a progressive and generalized vasculopathic condition associated with abnormal angiogenesis. We aim to determine whether changes in renal microvascular (MV) density correlate with and play a role in the progressive deterioration of renal function in diabetes. We hypothesize that MV changes represent the early steps of renal injury that worsen as diabetes progresses, initiating a vicious circle that leads to irreversible renal injury. Male nondiabetic (ND) or streptozotocin-induced diabetic (D) Sprague-Dawley rats were followed for 4 or 12 wk. Renal blood flow and glomerular filtration rate (GFR) were measured by PAH and 125I-[iothalamate], respectively. Renal MV density was quantified ex vivo using three-dimensional micro computed tomography and JG-12 immunoreactivity. Vascular endothelial growth factor (VEGF) levels (ELISA) and expression of VEGF receptors and factors involved in MV remodeling were quantified in renal tissue by Western blotting. Finally, renal morphology was investigated by histology. Four weeks of diabetes was associated with increased GFR, accompanied by a 34% reduction in renal MV density and augmented renal VEGF levels. However, at 12 wk, while GFR remained similarly elevated, reduction of MV density was more pronounced (75%) and associated with increased MV remodeling, renal fibrosis, but unchanged renal VEGF compared with ND at 12 wk. The damage, loss, and subsequent remodeling of the renal MV architecture in the diabetic kidney may represent the initiating events of progressive renal injury. This study suggests a novel concept of MV disease as an early instigator of diabetic kidney disease that may precede and likely promote the decline in renal function. PMID:22031855

Revascularization to preserve renal function in patients with atherosclerotic renovascular disease.

PubMed

Novick, A C; Textor, S C; Bodie, B; Khauli, R B

1984-08-01

There are a significant number of patients with advanced atherosclerotic renovascular disease whose blood pressure is well controlled with medical therapy but in whom such vascular disease poses a grave risk to overall renal function. This article reviews current concepts regarding screening, evaluation, and selection of patients with this disease for revascularization to preserve renal function. The underlying rationale for this approach is an increasing awareness that, in selected patients, atherosclerotic renovascular disease represents a surgically correctable cause of progressive renal failure.

Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges

PubMed Central

Shirazian, Shayan; Aina, Olufemi; Park, Youngjun; Chowdhury, Nawsheen; Leger, Kathleen; Hou, Linle; Miyawaki, Nobuyuki; Mathur, Vandana S

2017-01-01

Chronic kidney disease-associated pruritus (CKD-aP) is a distressing, often overlooked condition in patients with CKD and end-stage renal disease. It affects ~40% of patients with end-stage renal disease and has been associated with poor quality of life, poor sleep, depression, and mortality. Prevalence estimates vary based on the instruments used to diagnose CKD-aP, and standardized diagnostic instruments are sorely needed. Treatment studies have often yielded conflicting results. This is likely related to studies that are limited by small sample size, flawed designs, and nonstandardized diagnostic instruments. Several large well-designed treatment trials have recently been completed and may soon influence CKD-aP management. PMID:28176969

Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

PubMed

Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

2016-12-20

The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

Points to consider in renal involvement in systemic sclerosis.

PubMed

Galluccio, Felice; Müller-Ladner, Ulf; Furst, Daniel E; Khanna, Dinesh; Matucci-Cerinic, Marco

2017-09-01

This article discusses points to consider when undertaking a clinical trial to test therapy for renal involvement in SSc, not including scleroderma renal crisis. Double-blind, randomized controlled trials vs placebo or standard background therapy should be strongly considered. Inclusion criteria should consider a pre-specified range of renal functions or stratification of renal function. Gender and age limitations are probably not necessary. Concomitant medications including vasodilators, immunosuppressants and endothelin receptor antagonists and confounding illnesses such as diabetes, kidney stones, hypertension and heart failure need to be considered. A measure of renal function should be strongly considered, while time to dialysis, mortality, prevention of scleroderma renal crisis and progression of renal disease can also be considered, although they remain to be validated. Detailed, pre-planned analysis should be strongly considered and should include accounting for missing data. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adiponectin is not associated with renal function decline in community-dwelling elderly adults.

PubMed

Kobayashi, Hiroki; Otsuka, Hiromasa; Yanai, Mitsuru; Haketa, Akira; Hara, Motohiko; Hishiki, Mikano; Abe, Masanori; Soma, Masayoshi

2018-05-01

Adiponectin secreted by adipocytes plays an important role in the regulation of glucose and fatty acid metabolism. Contrary to findings in patients with chronic kidney disease (CKD), no prospective data about the association of serum adiponectin with renal function decline in the general population have yet appeared. Our objective was to analyze the relationship of total and high molecular weight (HMW) adiponectin with renal function decline as measured by cystatin C in community-dwelling elderly adults without moderate or severe CKD.In a prospective observational analysis, a total of 216 healthy elderly volunteers with eGFRcys ≥60 mL/min/1.73 m underwent anthropometric and laboratory tests at baseline and at follow-up visits. A subgroup with serum samples collected 5 years apart was further analyzed.There were no differences in either total or HMW adiponectin level between subjects subsequently undergoing rapid renal function decline and subjects with normal physiologic renal function decline (P = .71, P = .81). On univariate linear regression, neither total nor HMW adiponectin were associated with annual renal function decline (β = -0.23; P = .71, β = -0.057; P = .90). Multivariate analysis did not show a significant contribution of either total or HMW adiponectin to annual renal function decline (β = -0.50; P = .46, β = 0.01; P = .98). In the logistic regression analysis, we did not observe any statistically significant association of serum adiponectin levels with rapid renal function decline or incidence of CKD.Contrary to findings in populations with CKD, neither total nor HMW adiponectin had a substantial association with renal function decline in an elderly population with eGFRcys ≥60 mL/min/1.73 m. Our results and conclusions should not be extrapolated to subjects with other characteristics.

Influence of impairment in renal function on the accuracy of high-sensitivity cardiac troponin T for the diagnosis of perioperative myocardial infarction after heart valve surgery.

PubMed

Cubero-Gallego, Hector; Heredia-Rodriguez, Maria; Tamayo, Eduardo

2018-03-12

We aimed to assess the influence of impairment in renal function over the high-sensitivity cardiac troponin T (hs-cTnT) accuracy to diagnose perioperative myocardial infarction (MI) after heart valve surgery. Heart valve surgery was performed in 805 patients from June 2012 to January 2016. Patients with enzymatic curves of hs-cTnT suggestive of myocardial necrosis and electrocardiogram and/or transthoracic echocardiogram criteria were identified as patients with perioperative MI. Impairment in renal function was defined as a postoperative creatinine clearance <50 ml/min at 16 h after surgery and for at least 48 h. Patients included were divided into 2 groups at 16 h: (i) patients with normal renal function (creatinine clearance >50 ml/min) and (ii) patients with impairment in renal function (creatinine clearance <50 ml/min). From a total of 805 patients undergoing heart valve surgery, 88 patients developed perioperative MI. When comparing receiver operating characteristic curves in patients with perioperative MI according to renal function, the optimal threshold of hs-cTnT at 16 h differed in patients with impairment in renal function (1303 vs 1095 pg/ml, P < 0.001). The diagnostic accuracy of hs-cTnT at 16 h was 93.4% [95% confidence interval (CI) 89.98-96.86], with an area under receiver operating characteristic curve (0.993, 95% CI 0.988-0.999 vs 0.972, 95% CI 0.952-0.992; P < 0.001). Renal function might influence in hs-cTnT levels. However, a hs-cTnT threshold of 1303 pg/ml at 16 h may be applied according to renal function to diagnose perioperative MI after cardiac surgery.

Optimal management of renal cell carcinoma in the elderly: a review

PubMed Central

Quivy, Amandine; Daste, Amaury; Harbaoui, Asma; Duc, Sophie; Bernhard, Jean-Christophe; Gross-Goupil, Marine; Ravaud, Alain

2013-01-01

Both the aging population and the incidence of renal cell carcinoma (RCC) are growing, making the question of tumor management in the elderly a real challenge. Doctors should be aware of the importance of assessing this specific subpopulation. An aggressive therapeutic approach may be balanced by the benefit of the treatment — care or cure — and the life expectancy and willingness of the patient. The treatment for local disease can be surgery (radical or partial nephrectomy) or ablative therapies (radiofrequency, cryotherapy). Even if in most cases surgery is safe, complications such as alteration of renal function may occur, especially in the elderly, with physiological renal impairment at baseline. More recently, another option has been developed as an alternative: active surveillance. In the past decade, new drugs have been approved in the metastatic setting. All the phase 3 trials have included patients without a limit on age. Nevertheless, data concerning the elderly are still poor and concern only a very selective subpopulation. The toxicity profile of targeted agents may interfere with pre-existent comorbidities. Furthermore, the metabolism of several agents via cytochrome P450 can cause drug interaction. The importance of quality of life is a major factor with regard to management of therapy. Finally, to date, there is no recommendation of systematic a priori dose reduction in the elderly. In this review we describe the various possibilities of treatment for localized RCC or metastatic RCC in an aging population. PMID:23626463

[Asymptomatic Renal Stones: Do they really Exist?].

PubMed

Seseke, S; Rudolph, R; Rebmann, U

2011-11-01

Asymptomatic renal calculi without any history of colic, hematuria or infection can be found as an incidental finding during preven-tive check-ups. The aim of our study was to eval-uate whether these stones provoke symptoms with the need for further treatment during the follow-up and whether they cause cortical defects which may consecutively affect the renal func-tion. In a prospective study we evaluated 104  patients with renal calculi. The -medical history, radiological findings and functional imaging as well as urine and blood analyses were recorded and evaluated. The influence of stone size and localisation on the development of acute stone-related symptoms, renal function and renal scarring were evaluated. Furthermore, we analysed whether localised pathological findings in radiographic or functional imaging may influence the creatinine level. The follow-up was be-tween 12 and 48  months (median: 25  months). During the study period 27 / 104 of our patients (26 %) developed symptomatic events (renal colic, hematuria, infection) in which patients with middle pole calculi with a mean -cumulative stone diameter of 9.8  mm had the -highest risk. A localised renal scarring could be found in 36.6 %. These patients had a significantly higher risk in presenting an increased creatinine level. Increasing stone size was diagnosed in 39  cases (37.5 %). Asymptomatic renal stones have to be controlled regularly in order to prevent the -patient from loss of renal function and hypertension caused by increasing stones or urinary tract infection. © Georg Thieme Verlag KG Stuttgart ˙ New York.

Probability of reduced renal function after contrast-enhanced CT: a model based on serum creatinine level, patient age, and estimated glomerular filtration rate.

PubMed

Herts, Brian R; Schneider, Erika; Obuchowski, Nancy; Poggio, Emilio; Jain, Anil; Baker, Mark E

2009-08-01

The objectives of our study were to develop a model to predict the probability of reduced renal function after outpatient contrast-enhanced CT (CECT)--based on patient age, sex, and race and on serum creatinine level before CT or directly based on estimated glomerular filtration rate (GFR) before CT--and to determine the relationship between patients with changes in creatinine level that characterize contrast-induced nephropathy and patients with reduced GFR after CECT. Of 5,187 outpatients who underwent CECT, 963 (18.6%) had serum creatinine levels obtained within 6 months before and 4 days after CECT. The estimated GFR was calculated before and after CT using the four-variable Modification of Diet in Renal Disease (MDRD) Study equation. Pre-CT serum creatinine level, age, race, sex, and pre-CT estimated GFR were tested using multiple-variable logistic regression models to determine the probability of having an estimated GFR of < 60 and < 45 mL/min/1.73 m(2) after CECT. Two thirds of the patients were used to create and one third to test the models. We also determined discordance between patients who met standard definitions of contrast-induced nephropathy and those with a reduced estimated GFR after CECT. Significant (p < 0.002) predictors for a post-CT estimated GFR of < 60 mL/min/1.73 m(2) were age, race, sex, pre-CT serum creatinine level, and pre-CT estimated GFR. Sex, serum creatinine level, and pre-CT estimated GFR were significant factors (p < 0.001) for predicting a post-CT estimated GFR of < 45 mL/min/1.73 m(2). The probability is [exp(y) / (1 + exp(y))], where y = 6.21 - (0.10 x pre-CT estimated GFR) for an estimated GFR of < 60 mL/min/1.73 m(2), and y = 3.66 - (0.087 x pre-CT estimated GFR) for an estimated GFR of < 45 mL/min/1.73 m(2). A discrepancy between those who met contrast-induced nephropathy criteria by creatinine changes and those with a post-CT estimated GFR of < 60 mL/min/1.73 m(2) was detected in 208 of the 963 patients (21.6%). The probability of a reduced estimated GFR after CECT can be predicted by the pre-CT estimated GFR using the four-variable MDRD equation. Furthermore, standard criteria for contrast-induced nephropathy are poor predictors of poor renal function after CECT. Criteria need to be established for what is an acceptable risk to manage patients undergoing CECT.

Renal uptake of radioactive mercury (/sup 197/HgCl/sub 2/): method for testing the functional value of each kidney. Technique--results--and clinical application in urology and nephrology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raynaud, C.

The first three chapters consider measurement of mercury renal uptake by external counting, by quantitative scintigraphy, and by the gamma camera. Some topics discussed in the remaining 14 chapters are as follows: renal depth; phantoms; precautions regarding the liver, spleen, and intestine; stability of /sup 197/HgCl/sub 2/ solutions; use of mercury renal uptake in pediatric and adult urology; indications for mercury renal uptake in renal transplants; and appraisal of the radiological and chemical toxicity of /sup 197/HgCl/sub 2/. It was concluded that mercury renal uptake is an accurate and nontraumatizing method of measuring the functional value of each kidney. Itmore » makes it possible to determine whether a kidney is normal or pathological and to what extent its function is diminished or increased. (HLW)« less

Predictors of post-hospitalization recovery of renal function among patients with acute kidney injury requiring dialysis.

PubMed

Pajewski, Russell; Gipson, Patrick; Heung, Michael

2018-01-01

Acute kidney injury (AKI) requiring dialysis complicates 1% of all hospital admissions, and up to 30% of survivors will still require dialysis at hospital discharge. There is a paucity of data to describe the postdischarge outcomes or to guide evidence-based dialysis management of this vulnerable population. Single-center, retrospective analysis of 100 consecutive patients with AKI who survived to hospital discharge and required outpatient dialysis. Data collection included baseline characteristics, hospitalization characteristics, and outpatient dialysis treatment variables. Primary outcome was dialysis independence 90 days after discharge. Overall, 43% of patients recovered adequate renal function to discontinue dialysis, with the majority recovering within 30 days post discharge. Worse baseline renal function was associated with lower likelihood of renal recovery. In the first week postdischarge, patients with subsequent nonrecovery of renal function had greater net fluid removal (5.3 vs. 4.1 L, P = 0.037), higher ultrafiltration rates (6.0 vs. 4.7 mL/kg/h, P = 0.041) and more frequent intradialytic hypotension (24.6% vs. 9.3% with 3 or more episodes, P = 0.049) compared to patients that later recovered. A significant proportion of AKI survivors will recover renal function following discharge. Outpatient intradialytic factors may influence subsequent renal function recovery. © 2017 International Society for Hemodialysis.

The exciting "bench to bedside" journey of cell therapies for acute kidney injury and renal transplantation.

PubMed

Dellepiane, Sergio; Medica, Davide; Quercia, Alessandro Domenico; Cantaluppi, Vincenzo

2017-06-01

Acute kidney injury (AKI) is characterized by an increasing incidence and poor outcomes in both developed and undeveloped countries. AKI is also acquiring importance in the setting of kidney transplantation (KT): besides all the classical forms of AKI that KT patients may undergo, several transplant-specific injuries can also lead to the loss of graft function. The mechanisms of tissue damage in native and grafted kidneys share several common pathogenic elements. Since appropriate therapeutic treatments are still lacking-probably due to the disease complexity-clinicians are forced to provide only supportive care. In this composite scenario, cell therapies represent an evolving frontier for AKI treatment in native and transplanted kidneys: ex-vivo manipulated stem or immune cells are able to counteract renal dysfunction by a wide range of biological mechanisms. In this review, we will discuss the potential applications of cell therapies in AKI and KT by analyzing the available clinical data and the most promising experimental prospects from a "bench to bedside" perspective.

The Interplay between inflammation and fibrosis in kidney transplantation.

PubMed

Torres, Irina B; Moreso, Francesc; Sarró, Eduard; Meseguer, Anna; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.

The Interplay between Inflammation and Fibrosis in Kidney Transplantation

PubMed Central

Torres, Irina B.; Moreso, Francesc; Sarró, Eduard; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis. PMID:24991565

Neural control of renal function.

PubMed

Johns, Edward J; Kopp, Ulla C; DiBona, Gerald F

2011-04-01

The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure. © 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.

Ipsilateral renal function preservation after robot-assisted partial nephrectomy (RAPN): an objective analysis using mercapto-acetyltriglycine (MAG3) renal scan data and volumetric assessment.

PubMed

Zargar, Homayoun; Akca, Oktay; Autorino, Riccardo; Brandao, Luis Felipe; Laydner, Humberto; Krishnan, Jayram; Samarasekera, Dinesh; Stein, Robert J; Kaouk, Jihad H

2015-05-01

To objectively assess ipsilateral renal function (IRF) preservation and factors influencing it after robot-assisted partial nephrectomy (RAPN). Our database was queried to identify patients who had undergone RAPN from 2007 to 2013 and had complete pre- and postoperative mercapto-acetyltriglycine (MAG3) renal scan assessment. The estimated glomerular filtration rate (eGFR) for the operated kidney was calculated by multiplying the percentage of contribution from the renal scan by the total eGFR. IRF preservation was defined as a ratio of the postoperative eGFR for the operated kidney to the preoperative eGFR for the operated kidney. The percentage of total eGFR preservation was calculated in the same manner (postoperative eGFR/preoperative eGFR × 100). The amount of healthy rim of renal parenchyma removed was assessed by deducting the volume of tumour from the volume of the PN specimen assessed on pathology. Multivariable linear regression was used for analysis. In all, 99 patients were included in the analysis. The overall median (interquartile range) total eGFR preservation and IRF preservation for the operated kidney was 83.83 (75.2-94.1)% and 72 (60.3-81)%, respectively (P < 0.01). On multivariable analysis, volume of healthy rim of renal parenchyma removed, warm ischaemia time (WIT) > 30 min, body mass index (BMI) and operated kidney preoperative eGFR were predictive of IRF preservation. Using total eGFR tends to overestimate the degree of renal function preservation after RAPN. This is particularly relevant when studying factors affecting functional outcomes after nephron-sparing surgery. IRF may be a more precise assessment method in this setting. Operated kidney baseline renal function, BMI, WIT >30 min, and amount of resected healthy renal parenchyma represent the factors with a significant impact on the IRF preservation. RAPN provides significant preservation of renal function as shown by objective assessment criteria. © 2014 The Authors. BJU International © 2014 BJU International.

The natural history of renal function after surgical management of renal cell carcinoma: Results from the Canadian Kidney Cancer Information System.

PubMed

Mason, Ross; Kapoor, Anil; Liu, Zhihui; Saarela, Olli; Tanguay, Simon; Jewett, Michael; Finelli, Antonio; Lacombe, Louis; Kawakami, Jun; Moore, Ronald; Morash, Christopher; Black, Peter; Rendon, Ricardo A

2016-11-01

Patients who undergo surgical management of renal cell carcinoma (RCC) are at risk for chronic kidney disease and its sequelae. This study describes the natural history of renal function after radical and partial nephrectomy and explores factors associated with postoperative decline in renal function. This is a multi-institutional cohort study of patients in the Canadian Kidney Cancer Information System who underwent partial or radical nephrectomy for RCC. Estimated glomerular filtration rate (eGFR) and stage of chronic kidney disease were determined preoperatively and at 3, 12, and 24 months postoperatively. Linear regression was used to determine the association between postoperative eGFR and type of surgery (radical vs. partial), duration of ischemia, ischemia type (warm vs. cold), and tumor size. With a median follow-up of 26 months, 1,379 patients were identified from the Canadian Kidney Cancer Information System database including 665 and 714 who underwent partial and radical nephrectomy, respectively. Patients undergoing radical nephrectomy had a lower eGFR (mean = 19ml/min/1.73m 2 lower) at 3, 12, and 24 months postoperatively (P<0.001). Decline in renal function occurred early and remained stable throughout follow-up. A lower preoperative eGFR and increasing age were also associated with a lower postoperative eGFR (P<0.01). Ischemia type and duration were not predictive of postoperative decline in eGFR (P>0.05). Severe renal failure (eGFR<30ml/min/1.73m 2 ) developed postoperatively in 12.5% and 4.1% of radical and partial nephrectomy patients, respectively (P<0.001). After the initial postoperative decline, renal function remains stable in patients undergoing surgery for RCC. Patients undergoing radical nephrectomy have a greater long-term reduction in renal function compared with those undergoing partial nephrectomy. Ischemia duration and type are not predictive of postoperative renal function when adhering to generally short ischemia durations. Copyright © 2016 Elsevier Inc. All rights reserved.

Successful renal transplantation from a brain-dead deceased donor with head injury, disseminated intravascular coagulation and deranged renal functions.

PubMed

Ghuge, P P; Kute, V B; Vanikar, A V; Gumber, M R; Gera, D N; Patel, H V; Shah, P R; Modi, P R; Shah, V R; Trivedi, H L

2013-11-01

Deceased donors (DDs) with the brain death due to head injury are the major source of organs for transplantation. The incidence of post-head injury disseminated intravascular coagulation (DIC) ranges from 24% to 50%. Many centers do not accept organs from donors with DIC due to increased risk of primary graft non-function and/or high chances of morbidity/mortality. We performed two successful renal transplants from a DD with head injury with DIC and deranged renal function. One of the recipients developed transient thrombocytopenia, but there was no evidence of DIC or delayed graft functions in either of the recipients. Over a follow-up of 1 month, both are doing well with stable graft function and hematological profile. Thus, a carefully selected DD with severe DIC even with deranged renal function is not a contraindication for organ donation if other risk factors for primary non-function are excluded. This approach will also help in overcoming organ shortage.

[Robotic assisted laparoscopic living donor nephrectomy: preoperative assessment and results of 100 cases].

PubMed

Laplace, B; Ladrière, M; Claudon, M; Eschwege, P; Kessler, M; Hubert, J

2014-04-01

To assess short term morbidity and renal function after robotic laparoscopic living donor nephrectomy. We performed a retrospective analysis of 100 consecutives patients undergoing a robotic laparoscopic living donors nephrectomy. We analyzed isotopic measure of the renal function before and 4 months after surgery, the side, the number of arteries, the blood loss, the operative time and warm ischemia time. In the outcomes, we collected the complications, the length of stay, and for the receiver, the renal function recovery time, dialysis, survival and renal function at one year. Left kidney nephrectomy was performed in 85 patients and we observed 25 multiples renal arteries. Mean estimated blood loss was 0,8 g/dL. Mean operative time and warm ischemia time were respectively 174 ± 30 and 4.8 ± 1.7 minutes. Seven complications occured, with 2 major (Clavien-Dindo System). Mean length of stay was 5.1 ± 1.9 days. Mean glomerular filtration decrease was 26% and remains stable at one year after surgery. Grafts had an immediate renal function recovery for 99%, and were all functional after one year, with mean MDRD clearance of 57 ± 14mL/min. Robotic procedure in laparoscopic living donor nephrectomy seems to guarantee low morbidity and the stability of the renal function decrease of 26%. Copyright © 2013. Published by Elsevier Masson SAS.

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction.

PubMed

Hamamura, Kengo; Matsunaga, Naoya; Ikeda, Eriko; Kondo, Hideaki; Ikeyama, Hisako; Tokushige, Kazutaka; Itcho, Kazufumi; Furuichi, Yoko; Yoshida, Yuya; Matsuda, Masaki; Yasuda, Kaori; Doi, Atsushi; Yokota, Yoshifumi; Amamoto, Toshiaki; Aramaki, Hironori; Irino, Yasuhiro; Koyanagi, Satoru; Ohdo, Shigehiro

2016-03-04

Chronic kidney disease (CKD) is associated with an increase in serum retinol; however, the underlying mechanisms of this disorder are poorly characterized. Here, we found that the alteration of hepatic metabolism induced the accumulation of serum retinol in 5/6 nephrectomy (5/6Nx) mice. The liver is the major organ responsible for retinol metabolism; accordingly, microarray analysis revealed that the hepatic expression of most CYP genes was changed in 5/6Nx mice. In addition, D-box-binding protein (DBP), which controls the expression of several CYP genes, was significantly decreased in these mice. Cyp3a11 and Cyp26a1, encoding key proteins in retinol metabolism, showed the greatest decrease in expression in 5/6Nx mice, a process mediated by the decreased expression of DBP. Furthermore, an increase of plasma transforming growth factor-β1 (TGF-β1) in 5/6Nx mice led to the decreased expression of the Dbp gene. Consistent with these findings, the alterations of retinol metabolism and renal dysfunction in 5/6Nx mice were ameliorated by administration of an anti-TGF-β1 antibody. We also show that the accumulation of serum retinol induced renal apoptosis in 5/6Nx mice fed a normal diet, whereas renal dysfunction was reduced in mice fed a retinol-free diet. These findings indicate that constitutive Dbp expression plays an important role in mediating hepatic dysfunction under CKD. Thus, the aggravation of renal dysfunction in patients with CKD might be prevented by a recovery of hepatic function, potentially through therapies targeting DBP and retinol. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Versican Promotes Tumor Progression, Metastasis and Predicts Poor Prognosis in Renal Carcinoma.

PubMed

Mitsui, Yozo; Shiina, Hiroaki; Kato, Taku; Maekawa, Shigekatsu; Hashimoto, Yutaka; Shiina, Marisa; Imai-Sumida, Mitsuho; Kulkarni, Priyanka; Dasgupta, Pritha; Wong, Ryan Kenji; Hiraki, Miho; Arichi, Naoko; Fukuhara, Shinichiro; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Deng, Guoren; Dahiya, Rajvir; Nakajima, Koichi; Tanaka, Yuichiro

2017-07-01

The proteoglycan versican (VCAN) promotes tumor progression and enhances metastasis in several cancers; however, its role in clear cell renal cell carcinoma (ccRCC) remains unknown. Recent evidence suggests that VCAN is an important target of chromosomal 5q gain, one of the most prevalent genetic abnormalities in ccRCC. Thus, we investigated whether VCAN expression is associated with the pathogenesis of ccRCC. VCAN expression was analyzed using three RCC and normal kidney cell lines as well as a clinical cohort of 84 matched ccRCC and normal renal tissues. Functional analyses on growth and progression properties were performed using VCAN-depleted ccRCC cells. Microarray expression profiling was employed to investigate the target genes and biologic pathways involved in VCAN-mediated ccRCC carcinogenesis. ccRCC had elevated VCAN expression in comparison with normal kidney in both cell lines and clinical specimens. The elevated expression of VCAN was significantly correlated with metastasis ( P < 0.001) and worse 5-year overall survival after radical nephrectomy ( P = 0.014). In vitro , VCAN knockdown significantly decreased cell proliferation and increased apoptosis in Caki-2 and 786-O cells, and this was associated with alteration of several TNF signaling-related genes such as TNFα, BID , and BAK Furthermore, VCAN depletion markedly decreased cell migration and invasion which correlated with reduction of MMP7 and CXCR4. These results demonstrate that VCAN promotes ccRCC tumorigenesis and metastasis and thus is an attractive target for novel diagnostic, prognostic, and therapeutic strategies. Implications: This study highlights the oncogenic role of VCAN in renal cell carcinogenesis and suggests that this gene has therapeutic and/or biomarker potential for renal cell cancer. Mol Cancer Res; 15(7); 884-95. ©2017 AACR . ©2017 American Association for Cancer Research.

Etiology and outcome of acute renal failure in pregnancy.

PubMed

Hassan, Irfana; Junejo, Abdul Manan; Dawani, Manohar Lal

2009-11-01

To determine the etiology and outcome of Acute Renal Failure (ARF) in pregnancy. A case series. Nephrology Department of the Jinnah Postgraduate Medical Centre, Karachi, from August 2007 to July 2008. Pregnant women who were healthy previously and had developed ARF, diagnosed on oliguria (urine output <400 ml/day) and mounting azotemia (serum creatinine > 2 mg%) were included in the study. Percutaneous renal biopsy was performed for delayed recovery, i.e. after three weeks. Patients were followed up for a period of 6 months. Percentages were calculated for qualitative variables i.e. causes of ARF, mortality, morbidity and outcome in form of complete recovery, partial recovery, demise and non-recovery. A total of 43 patients with pregnancy-related ARF were included in the study. The puerperal group comprised 36 patients (83.7%). Haemorrhage was the etiology for ARF in 25 (58.1%), antepartum haemorrhage APH in 8 (18.6%) and postpartum haemorrhage PPH in 16 (37.2%) of patients. In 12 (27.9%), puerperal sepsis was the etiological factor, while 4 (9.3%) patients had DIC on presentation. Pre-eclampsia, eclampsia and HELLP syndrome accounted for 5 (11.6%). While 1 (2.3%) was diagnosed with hemolytic uremic syndrome and another one was diagnosed as ARF secondary to hypotension produced by hyperemesis gravidarum. Renal biopsy was performed in 31 patients showing that 10 had acute cortical necrosis and 21 had acute tubular necrosis. Maternal mortality was 16.2% (n=7). Of the 36 (83.7%) surviving patients, 18 (41.4%) had complete recovery of renal function; 12 (27.9%) had partial recovery; and 6 (13.9%) required chronic dialysis. Pregnancy-related ARF was associated with poor outcome. Antepartum and postpartum haemorrhage were the most common cause of ARF in pregnancy.

Essentials of equine renal and urinary tract physiology.

PubMed

Toribio, Ramiro E

2007-12-01

Knowledge of urinary tract anatomy and the numerous functions of the kidney in regulating fluids, electrolytes, acid-base balance, and waste products improves the ability of the clinician to diagnose, treat, and make appropriate recommendations for the management of the horse with renal disease. Several conditions can directly or indirectly affect renal function on a temporary or permanent basis. Endogenous and exogenous compounds (eg, drugs, toxins, hemoglobin) alone or in combination with inappropriate renal blood flow can promote or exacerbate renal disease.

A unified pathogenesis for kidney diseases, including genetic diseases and cancers, by the protein-homeostasis-system hypothesis.

PubMed

Lee, Kyung-Yil

2017-06-01

Every cell of an organism is separated and protected by a cell membrane. It is proposed that harmony between intercellular communication and the health of an organism is controlled by a system, designated the protein-homeostasis-system (PHS). Kidneys consist of a variety of types of renal cells, each with its own characteristic cell-receptor interactions and producing characteristic proteins. A functional union of these renal cells can be determined by various renal function tests, and harmonious intercellular communication is essential for the healthy state of the host. Injury to a kind of renal cells can impair renal function and induce an imbalance in total body health. Every acute or chronic renal disease has unknown etiologic substances that are responsible for renal cell injury at the molecular level. The immune/repair system of the host should control the etiologic substances acting against renal cells; if this system fails, the disease progresses to end stage renal disease. Each renal disease has its characteristic pathologic lesions where immune cells and immune proteins, such as immunoglobulins and complements, are infiltrated. These immune cells and immune proteins may control the etiologic substances involved in renal pathologic lesions. Also, genetic renal diseases and cancers may originate from a protein deficiency or malfunctioning protein under the PHS. A unified pathogenesis for renal diseases, including acute glomerulonephritis, idiopathic nephrotic syndrome, immunoglobulin A nephropathy, genetic renal diseases such as Alport syndrome, and malignancies such as Wilms tumor and renal cell carcinoma, is proposed using the PHS hypothesis.

Arterial stiffness and decline of renal function in a primary care population.

PubMed

van Varik, Bernard J; Vossen, Liv M; Rennenberg, Roger J; Stoffers, Henri E; Kessels, Alfons G; de Leeuw, Peter W; Kroon, Abraham A

2017-01-01

Arterial stiffness is an important pathophysiological factor linking cardiovascular disease and kidney disease. Controversy exists as to whether arterial stiffness causes renal function decline, or kidney dysfunction leads to stiffening or whether the association is mutual. We aimed to investigate the longitudinal association between arterial stiffness and annual rate of renal function decline. We prospectively investigated in a primary care population whether carotid-femoral pulse wave velocity (PWV) was associated with estimated glomerular filtration rate (eGFR) and annual decline in eGFR in participants aged ⩾40 years without overt kidney disease. Baseline data on PWV and eGFR were available for 587 participants; follow-up measurements with a mean duration of 5.6 years were available for 222 patients. PWV, female gender and mean arterial pressure were independently associated with eGFR at baseline, although age confounded this association. More importantly, baseline PWV, age and eGFR were independent predictors of renal function decline. Stratification for age showed that the effect of PWV on rate of eGFR decline was amplified with advancing age. On the other hand, baseline eGFR did not determine annual change in PWV, suggesting a unidirectional association between arterial stiffness and eGFR. Arterial stiffness amplifies age-related renal function decline, suggesting that arterial stiffness plays a causal role in the development of renal damage, at least at later stages of age-related renal function decline, possibly through impaired renal autoregulation and increased arterial blood pressure pulsatility.

Cutting Balloon Angioplasty (CBA) for the Treatment of Renal Artery Fibromuscular Dysplasia (FMD) in Six Patients: 5-Year Long-Term Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cotroneo, Antonio Raffaele; Amoroso, Luigi; Giammarino, Alberto

PurposeTo evaluate long-term outcomes in terms of hypertension control, recurrent stenosis, and reinterventions from patients who underwent cutting balloon angioplasty (CBA) for symptomatic renal artery fibromuscular dysplasia (FMD).Materials and MethodsFrom 2011, six consecutive renal artery FMD women underwent CBA for poorly controlled hypertension, despite antihypertensive therapy. Follow-up consisted of blood pressure monitoring and duplex ultrasonography at 1, 6, and 12 months and thereafter annually for 5 years.ResultsAll treatments were technically successful. Recurrence of hypertension was found in two patients within 12 months, and reinterventions were performed using CBA.ConclusionResults show the efficacy of CBA for renal artery FMD.

Atypical cells in a voided urine cytology specimen in a renal transplant recipient.

PubMed

Lu, Miao; Ho, Julie; Azordegan, Nazila; Perry, Anamarija M; Gibson, Ian W; Baker, Patricia

2017-01-01

Voided urine is routinely collected from renal transplant patients to screen for polyomavirus. In rare cases, atypical lymphoid cells can be detected in voided urine and raise the suspicion of post-transplant lymphoproliferative disorder (PTLD). However, further immunohistochemistry of the cell block and flow cytometry is frequently limited by the low cellularity and poor preservation of voided urine. Therefore, PTLD of the renal allograft is usually diagnosed from tissue biopsy or nephrectomy specimens. Herein, we report a rare case of atypical cells in a voided urine cytology specimen from a kidney transplant recipient. Needle core biopsy of the renal allograft showed monomorphic PTLD. Diagn. Cytopathol. 2017;45:69-72. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Causes and correlates of anemia in 200 patients with acute cardiogenic pulmonary edema.

PubMed

Rovellini, Angelo; Graziadei, Giovanna; Folli, Christian; Brambilla, Anna Maria; Cosentini, Roberto; Canetta, Ciro; Monzani, Valter

2012-12-01

Acute heart failure has a poor prognosis and the presence of anemia may increase the risk of adverse outcomes. However, the clinical and laboratory characteristics of anemia in acute heart failure are poorly known. We aimed to assess the causes and the clinical and laboratory correlates of anemia in patients with acute cardiogenic pulmonary edema (ACPE). This observational study, performed in an Emergency Unit, enrolled 200 patients treated with medical therapy and continuous positive airway pressure. Anemia was found in 36% of patients (38.5% of females and 32.5% of males) and was severe (hemoglobin <9 g/dL) in 6.9% of cases. The most frequent causes of anemia were chronic renal failure (27.8%), chronic inflammatory states (27.8%) and the clustering of multiple factors (18.1%). A wider spectrum of etiological factors was found in females than in males. Microcytic anemia was observed only in females (20% of those anemic), mainly due to iron deficiency/chronic blood loss. Glomerular filtration rate, serum iron, serum albumin, total cholesterol and diastolic blood pressure were independently associated with hemoglobin levels. The etiology of anemia in ACPE is heterogeneous, with several causal factors besides impaired renal function. The pattern of anemia is different between genders, suggesting that sex-specific diagnostic and therapeutic targets should be implemented. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

PubMed

Choi, Don Kyoung; Jung, Se Bin; Park, Bong Hee; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

2015-10-01

We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (p=0.012), diabetes mellitus (p=0.023), hypertension (p=0.015) and chronic kidney disease stage (p <0.001). Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The use of fibrous, supramolecular membranes and human tubular cells for renal epithelial tissue engineering: towards a suitable membrane for a bioartificial kidney.

PubMed

Dankers, Patricia Y W; Boomker, Jasper M; Huizinga-van der Vlag, Ali; Smedts, Frank M M; Harmsen, Martin C; van Luyn, Marja J A

2010-11-10

A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We hypothesized that this can be improved by electro-spun, supramolecular polymer membranes which show clear benefits in ease of processability. We found that after 7 d, in comparison to conventional microporous membranes, renal tubular cells cultured on top of our fibrous supramolecular membranes formed polarized monolayers, which is prerequisite for a well-functioning bioartificial kidney. In future, these supramolecular membranes allow for incorporation of peptides that may increase cell function even further.

Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Cefiderocol, a Parenteral Siderophore Cephalosporin, for Dose Adjustment Based on Renal Function.

PubMed

Katsube, Takayuki; Wajima, Toshihiro; Ishibashi, Toru; Arjona Ferreira, Juan Camilo; Echols, Roger

2017-01-01

Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. Since cefiderocol is excreted primarily via the kidneys, this study was conducted to develop a population pharmacokinetics (PK) model to determine dose adjustment based on renal function. Population PK models were developed based on data for cefiderocol concentrations in plasma, urine, and dialysate with a nonlinear mixed-effects model approach. Monte-Carlo simulations were conducted to calculate the probability of target attainment (PTA) of fraction of time during the dosing interval where the free drug concentration in plasma exceeds the MIC (T f >MIC ) for an MIC range of 0.25 to 16 μg/ml. For the simulations, dose regimens were selected to compare cefiderocol exposure among groups with different levels of renal function. The developed models well described the PK of cefiderocol for each renal function group. A dose of 2 g every 8 h with 3-h infusions provided >90% PTA for 75% T f >MIC for an MIC of ≤4 μg/ml for patients with normal renal function, while a more frequent dose (every 6 h) could be used for patients with augmented renal function. A reduced dose and/or extended dosing interval was selected for patients with impaired renal function. A supplemental dose immediately after intermittent hemodialysis was proposed for patients requiring intermittent hemodialysis. The PK of cefiderocol could be adequately modeled, and the modeling-and-simulation approach suggested dose regimens based on renal function, ensuring drug exposure with adequate bactericidal effect. Copyright © 2016 American Society for Microbiology.

Increasing Body Mass Index Predicts Rapid Decline in Renal Function: A 5 Year Retrospective Study.

PubMed

Ma, Xiaojing; Zhang, Chengyin; Su, Hong; Gong, Xiaojie; Kong, Xianglei

2018-05-02

While obesity is a recognized risk factor for chronic kidney disease, it remains unclear whether change in body mass index (ΔBMI ) is independently associated with decline in renal function (evaluated by the change in estimated glomerular filtration rate, ΔeGFR) over time. Accordingly, to help clarify this we conducted a retrospective study to measure the association of ΔBMI with decline in renal function in Chinese adult population. A total of 4007 adults (aged 45.3±13.7 years, 68.6% male) without chronic kidney disease at baseline were enrolled between 2008 and 2013. Logistic regression models were applied to explore the relationships between baseline BMI and ΔBMI, and rapid decline in renal function (defined as the lowest quartile of ΔeGFR ). During 5 years of follow-up, the ΔBMI and ΔeGFR were 0.47±1.6 (kg/m 2 ) and -3.0±8.8 (ml/min/1.73 m 2 ), respectively. After adjusted for potential confounders, ΔBMI (per 1 kg/m 2 increase) was independently associated with the rapid decline in renal function [with a fully adjusted OR of 1.12 (95% CI, 1.05 to 1.20). By contrast, the baseline BMI was not associated with rapid decline in renal function [OR=1.05 (95% CI, 0.98 to 1.13)]. The results were robust among 2948 hypertension-free and diabetes-free participants, the adjusted ORs of ΔBMI and baseline BMI were 1.14 (95% CI, 1.05 to 1.23) and 1.0 (95% CI, 0.96 to 1.04) for rapid decline in renal function, respectively. The study revealed that increasing ΔBMI predicts rapid decline in renal function. © Georg Thieme Verlag KG Stuttgart · New York.

Cigarette smoking reduced renal function deterioration in hypertensive patients may be mediated by elevated homocysteine.

PubMed

Huang, Feifei; Chen, Jie; Liu, Xun; Han, Feng; Cai, Qingqing; Peng, Guicheng; Zhang, Kun; Chen, Weiqing; Wang, Jingfeng; Huang, Hui

2016-12-27

Elevated homocysteine (HCY) and smoking are both important risk factors for hypertensive patients. However, whether they have crossing effect on renal function deterioration of hypertensive patients and what is the underlying mechanism are unclear. In the present study, 3033 participants diagnosed as essential hypertension with estimated glomerular filtration rate (eGFR)> 30 ml/min/1.73 m2 from southern China were enrolled in this cross-sectional study. We collected the demographic and clinical data. In addition, the mediation effects were analyzed. The results showed that, comparing with non-smokers, smokers had significant higher levels of HCY (13.10 (11.20-16.87) vs. 11.00 (8.90-13.40) umol/L, P < 0.001) and lower eGFR (79.71 (66.83-91.05) vs. 82.89 (69.80-95.85) ml/min/1.73m2, P < 0.001). HCY levels and smoking were independently associated with decreased eGFR. Meanwhile, eGFR levels were significantly negatively correlated with HCY (P < 0.001), and this correlation might be stronger in current smokers. Current smoker consuming over 20 cigarettes per day would accelerate early renal function deterioration (OR = 1.859, P = 0.019). The mediation effects analysis further showed that the association between smoking and renal function deterioration was mediated by HCY. And elevated HCY was accounted for 56.94% of the estimated causal effect of smoking on renal function deterioration in hypertensive patients. Our findings indicated that cigarette smoking was associated with renal function deterioration in hypertensive patients, and the association between cigarette smoking and renal function deterioration was probably mediated by elevated HCY. Therefore, HCY-lowering therapy may be beneficial for renal function deterioration in hypertensive smoking patients.

Meta-analysis of safety and efficacy for direct oral anticoagulation treatment of non-valvular atrial fibrillation in relation to renal function.

PubMed

Zou, Rongjun; Tao, Jun; Shi, Wanting; Yang, Minglei; Li, Hongmu; Lin, Xifeng; Yang, Songran; Hua, Ping

2017-12-01

We performed a meta-analysis of the safety and efficacy of anticoagulation treatment for atrial fibrillation (AF) in relation to renal function. We also examined the change in estimated glomerular filtration rate (eGFR) from baseline and compared the outcomes for patients with stable and worsening renal function. We selected studies that used randomized controlled trials in which outcomes for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, or edoxaban) were compared with those for warfarin in AF patients with normal, mild or moderate renal function, except the severe one (creatinine clearance<30). We assessed five clinical trials, involving 72,608 patients. Pooled analysis indicated that the risk of stroke was lower for DOACs than for warfarin among patients with mild renal impairment (Risk ratio, 0.79; 95% confidence interval, 0.68-0.91) and moderate renal impairment (0.80, 0.69-0.92). No major differences were found in patients with normal renal function. Additionally, DOACs were associated with fewer major bleeds among patients with normal (0.77, 0.70-0.84), mild (0.86, 0.77-0.95), and moderate renal impairment (0.73, 0.65-0.82). Among those treated with DOACs, a lower dosage was associated with lower risk of major bleeding (0.75, 0.68-0.83) and higher risk of stroke or systemic embolism (1.28, 1.12-1.47). Further, DOACs tended to be associated with a lower estimated glomerular filtration rate (eGFR) than warfarin even after 30months. Finally, we found significant differences in the risk of stroke (2.09, 1.64-2.68) and major bleeding (2.01, 1.66-2.42) between patients with stable and worsening renal function. DOACs have a greater clinical benefit than warfarin with respect to renal function. They are associated with a comparatively lower risk of stroke and major bleeding, as well lower eGFR. This suggests these agents are a better choice in patients with renal disease. Copyright © 2017. Published by Elsevier Ltd.

Calpain-mediated proteolysis of polycystin-1 C-terminus induces JAK2 and ERK signal alterations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hyunho; Department of Medicine, University of Maryland, Baltimore, MD; Kang, Ah-Young

2014-01-01

Autosomal dominant polycystic kidney disease (ADPKD), a hereditary renal disease caused by mutations in PKD1 (85%) or PKD2 (15%), is characterized by the development of gradually enlarging multiple renal cysts and progressive renal failure. Polycystin-1 (PC1), PKD1 gene product, is an integral membrane glycoprotein which regulates a number of different biological processes including cell proliferation, apoptosis, cell polarity, and tubulogenesis. PC1 is a target of various proteolytic cleavages and proteosomal degradations, but its role in intracellular signaling pathways remains poorly understood. Herein, we demonstrated that PC1 is a novel substrate for μ- and m-calpains, which are calcium-dependent cysteine proteases. Overexpressionmore » of PC1 altered both Janus-activated kinase 2 (JAK2) and extracellular signal-regulated kinase (ERK) signals, which were independently regulated by calpain-mediated PC1 degradation. They suggest that the PC1 function on JAK2 and ERK signaling pathways might be regulated by calpains in response to the changes in intracellular calcium concentration. - Highlights: • Polycystin-1 is a target of ubiquitin-independent degradation by calpains. • The PEST domain is required for calpain-mediated degradation of polycystin-1. • Polycystin-1 may independently regulate JAK2 and ERK signaling pathways.« less

Safe Use of Contrast Media: What the Radiologist Needs to Know.

PubMed

Beckett, Katrina R; Moriarity, Andrew K; Langer, Jessica M

2015-10-01

Iodinated and gadolinium-based contrast media are used on a daily basis in most radiology practices. These agents often are essential to providing accurate diagnoses, and are nearly always safe and effective when administered correctly. However, reactions to contrast media do occur and can be life threatening. Therefore, it is critical for faculty and staff to know how reactions to contrast agents manifest and how to treat them promptly. The decline in renal function seen occasionally after intravenous administration of iodinated contrast agents is poorly understood and likely multifactorial, and its association with the contrast medium may be overemphasized. However, it is important that radiologists be aware of current understanding and strategies to decrease the incidence of renal dysfunction. Nephrogenic systemic fibrosis, a skin disease, is an adverse reaction related to use of some gadolinium-based contrast agents in patients with chronic renal failure. The types of gadolinium most often associated with this condition and the indications for withholding gadolinium are important and are discussed in this article. The use of enteric contrast agents and contrast agents during pregnancy and nursing are reviewed briefly. Current knowledge for safe use of contrast media and key concepts that all radiologists should know are summarized in this review. © RSNA, 2015.

Spectra-first feature analysis in clinical proteomics - A case study in renal cancer.

PubMed

Goh, Wilson Wen Bin; Wong, Limsoon

2016-10-01

In proteomics, useful signal may be unobserved or lost due to the lack of confident peptide-spectral matches. Selection of differential spectra, followed by associative peptide/protein mapping may be a complementary strategy for improving sensitivity and comprehensiveness of analysis (spectra-first paradigm). This approach is complementary to the standard approach where functional analysis is performed only on the finalized protein list assembled from identified peptides from the spectra (protein-first paradigm). Based on a case study of renal cancer, we introduce a simple spectra-binning approach, MZ-bin. We demonstrate that differential spectra feature selection using MZ-bin is class-discriminative and can trace relevant proteins via spectra associative mapping. Moreover, proteins identified in this manner are more biologically coherent than those selected directly from the finalized protein list. Analysis of constituent peptides per protein reveals high expression inconsistency, suggesting that the measured protein expressions are in fact, poor approximations of true protein levels. Moreover, analysis at the level of constituent peptides may provide higher resolution insight into the underlying biology: Via MZ-bin, we identified for the first time differential splice forms for the known renal cancer marker MAPT. We conclude that the spectra-first analysis paradigm is a complementary strategy to the traditional protein-first paradigm and can provide deeper level insight.

Biomarkers of Renal Tumor Burden and Progression in TSC

DTIC Science & Technology

2012-09-01

code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Biomarkers of Renal Tumor Burden and Progression in TSC Dr. Elahna Paul 1...appearance and growth rates) and renal function parameters (e.g. blood pressure, serum chemistries, urinalysis and urine chemistries). (2) Measure...and renal function parameters (e.g. blood pressure, serum chemistries, urinalysis and urine chemistries). (2) Measure soluble growth factors

Renal function following xenon anesthesia for partial nephrectomy-An explorative analysis of a randomized controlled study.

PubMed

Stevanovic, Ana; Schaefer, Patrick; Coburn, Mark; Rossaint, Rolf; Stoppe, Christian; Boor, Peter; Pfister, David; Heidenreich, Axel; Christ, Hildegard; Hellmich, Martin; Fahlenkamp, Astrid V

2017-01-01

Perioperative preservation of renal function has a significant impact on morbidity and mortality in kidney surgery. Nephroprotective effects of the anesthetic xenon on ischemia-reperfusion injury were found in several experimental studies. We aimed to explore whether xenon anesthesia can reduce renal damage in humans undergoing partial nephrectomy and to gather pilot data of possible nephroprotection in these patients. A prospective randomized, single-blinded, controlled study. Single-center, University Hospital of Aachen, Germany between July 2013-October 2015. Forty-six patients with regular renal function undergoing partial nephrectomy. Patients were randomly assigned to receive xenon- (n = 23) or isoflurane (n = 23) anesthesia. Primary outcome was the maximum postoperative glomerular filtration rate (GFR) decline within seven days after surgery. Secondary outcomes included intraoperative and tumor-related data, assessment of further kidney injury markers, adverse events and optional determination of renal function after 3-6 months. Unexpected radical nephrectomy was performed in 5 patients, thus they were excluded from the per-protocol analysis, but included in the intention-to-treat analysis. The maximum postoperative GFR decline was attenuated by 45% in the xenon-group (10.9 ml min-1 1.73 cm-2 versus 19.7 ml min-1 1.73 cm-2 in the isoflurane group), but without significance (P = 0.084). Occurrence of adverse events was reduced (P = 0.003) in the xenon group. Renal function was similar among the groups after 3-6 months. Xenon anesthesia was feasible and safe in patients undergoing partial nephrectomy with regard to postoperative renal function. We found no significant effect on early renal function but less adverse events in the xenon group. Larger randomized controlled studies in more heterogeneous collectives are required, to confirm or refute the possible clinical benefit on renal function by xenon. ClinicalTrials.gov NCT01839084 and EudraCT 2012-005698-30.

Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction.

PubMed

Gori, Mauro; Senni, Michele; Gupta, Deepak K; Charytan, David M; Kraigher-Krainer, Elisabeth; Pieske, Burkert; Claggett, Brian; Shah, Amil M; Santos, Angela B S; Zile, Michael R; Voors, Adriaan A; McMurray, John J V; Packer, Milton; Bransford, Toni; Lefkowitz, Martin; Solomon, Scott D

2014-12-21

Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higher NT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with low eGFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P < 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P < 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Acute and chronic effects of the insecticide endrin on renal function and renal hemodynamics.

DOT National Transportation Integrated Search

1963-10-01

Chronic and acute effects of the insecticide endrin on renal function were studied in dogs. Animals were exposed to endrin chronically by intramuscular injection and acutely by intravenous infusion. In acute studies dogs developed systemic hypertensi...

Neural control of renal function in health and disease.

PubMed

DiBona, G F

1994-04-01

The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.

Evaluation of renal function change during first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma.

PubMed

Ishihara, Hiroki; Kondo, Tsunenori; Fukuda, Hironori; Yoshida, Kazuhiko; Omae, Kenji; Takagi, Toshio; Iizuka, Junpei; Kobayashi, Hirohito; Tanabe, Kazunari

2017-12-01

The change in renal function induced by first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma remains unclear. One hundred and thirty-four patients were evaluated. Sunitinib (SU) and sorafenib (SO) were administered to 91 (67.9%) and 43 (32.1%) patients, respectively. The change in estimated glomerular filtration rate (ΔeGFR) was calculated as [(eGFR at each time point - pre-treatment eGFR)/pre-treatment eGFR] × 100. ΔeGFR was compared between SU- and SO users using a mixed-effects model for repeated measures data with two or greater. Additionally, predictors for ΔeGFR ≤ -10% at 6 months after therapy initiation were evaluated using multivariate logistic regression analysis. Throughout the 24 months after therapy initiation, ΔeGFR was negatively greater in SU users, compared with that in SO users (P < 0.0001). In SU users, renal dysfunction was observed regardless of pre-treatment chronic kidney disease (CKD) status, whereas the magnitude of renal dysfunction was milder in SO users. In SO users without pre-treatment CKD, renal function did not significantly deteriorate. Moreover, ΔeGFR ≤ -10% was more frequently observed in SU users after 3 months (P = 0.0121) and 6 months (P = 0.0009). Finally, SU usage was an independent predictor for ΔeGFR ≤ -10% at 6 months (odds ratio 8.87, P = 0.0053), along with pre-treatment hypertension (odds ratio 4.69, P = 00072). Deterioration of renal function was stronger with SU than SO. During SU therapy, renal function should be monitored and pre-treatment kidney function should be taken into consideration for therapy selection. © The Author 2017. Published by Oxford University Press.

Histological findings in two renal transplants accomplishing operational tolerance criteria

PubMed Central

Azancot, M.A.; Cantarell, C.; Torres, I.B.; Serón, D.R.

2011-01-01

Operational tolerance is defined as stable renal function in transplants without immunosuppression for at least 1 year. We present histological assessments of two patients with operational tolerance. The first withdrew immunosuppression in 2005 and presents stable renal function (creatinine 1.5 mg/dL) without proteinuria. The biopsy showed mild chronic tubulointerstitial changes without inflammation. The second withdrew immunosuppression in 2009 and maintains stable renal function (creatinine 1.6 mg/dL) with mild proteinuria. Histology showed chronic humoural rejection and Class II anti-human leukocyte antigen antibodies were detected. These cases suggest that a renal biopsy may be useful to rule out subclinical pathology in patients with operational tolerance. PMID:25984157

Histological findings in two renal transplants accomplishing operational tolerance criteria.

PubMed

Azancot, M A; Moreso, F; Cantarell, C; Torres, I B; Serón, D R

2011-06-01

Operational tolerance is defined as stable renal function in transplants without immunosuppression for at least 1 year. We present histological assessments of two patients with operational tolerance. The first withdrew immunosuppression in 2005 and presents stable renal function (creatinine 1.5 mg/dL) without proteinuria. The biopsy showed mild chronic tubulointerstitial changes without inflammation. The second withdrew immunosuppression in 2009 and maintains stable renal function (creatinine 1.6 mg/dL) with mild proteinuria. Histology showed chronic humoural rejection and Class II anti-human leukocyte antigen antibodies were detected. These cases suggest that a renal biopsy may be useful to rule out subclinical pathology in patients with operational tolerance.

Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

PubMed Central

Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

2012-01-01

Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

PubMed

Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

2012-08-01

Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

Safety of Direct-Acting Antiviral Therapy Regarding Renal Function in Post-Liver Transplant Patients Infected with Hepatitis C Virus and a 100% 12-Week Sustained Virologic Response-A Single-Center Study.

PubMed

Peschel, G; Moleda, L; Baier, L; Selgrad, M; Schmid, S; Scherer, M N; Müller, M; Weigand, K

2018-06-01

Patients after liver transplantation (LT) with hepatitis C virus (HCV) infection often suffer from renal or hepatic impairment. Treating patients after LT with direct-acting antivirals (DAA) might result in decreasing renal function due to interaction of DAA and immunosuppressive therapy. In this single-center study we analyzed clinical parameters of 18 HCV-infected patients treated with DAA therapy after LT. The primary end points were change of renal function (glomerular filtration rate) and sustained virologic response 12 weeks after therapy (SVR12). For secondary end points, we investigated the influence of DAA therapy on transaminases, bilirubin, international normalized ratio, noninvasive fibrosis measurement, and Model for End-Stage Liver Disease (MELD) score. Five out of 18 patients treated with DAA suffered from renal impairment stage 2, and 7 patients of renal impairment stage 3. Renal function at SVR12 was not influenced by preexisting renal impairment (P > .5), type of immunosuppressant (P > .5), or type of DAA regimen (P > .5). All patients reached SVR12. The levels of transaminases and bilirubin declined rapidly, as expected. Ten out of 18 patients already suffered from cirrhosis or liver fibrosis >F3 according to noninvasive measurement before initiation of treatment. Single-point acoustic radiation force impulse imaging improved in 9 patients (P = .012). In 7 patients, MELD score improved owing to the decrease of bilirubin levels. In 6 patients it worsened. DAA therapy in LT patients was effective and safe in this single-center real-life cohort. Renal function was not influenced by the administered drug combinations, even in patients with preexisting renal impairment. Copyright © 2018. Published by Elsevier Inc.

Long-term verification of functional and structural renal damage after renal sympathetic denervation.

PubMed

Dörr, Oliver; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Troidl, Christian; Wiebe, Jens; Renker, Matthias; Bauer, Timm; Hamm, Christian; Nef, Holger

2016-06-01

Previous studies of renal sympathetic denervation (RSD) excluded patients with impaired renal function to avoid potential RSD-related renal damage. Measurement of the highly sensitive biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) has shown that RSD does not aggravate renal damage during the early post-procedural period. The aim of the present study was to examine the effect of RSD on blood pressure (BP) reduction and renal function after a long-term follow-up. A total of 62 consecutive patients undergoing RSD were included in this study. Serum NGAL and KIM-1 were collected prior to RSD and at 24 hr, 48 hr, and 3 months after RSD. BP measurements, antihypertensive medication use, and safety events were followed over a three-year period. Follow-up data were available over 36.9[±3.4] months in 47 of 62 (75.8%) of the initially included patients. At this time point a significant systolic BP reduction of 23 mm Hg (P > 0.001) was documented, and there were no significant changes in serum creatinine (P = 0.14), blood urea nitrogen (P = 0.33), or estimated glomerular filtration rate (eGFR) (P = 0.2) values. There were also no significant changes documented in patients with impaired renal function (eGFR < 45 mL/min) during the early post- procedural period or the long-term follow-up (P = 0.34). The results of the present study show a sustained effect of RSD on BP reduction after a three-year follow-up, and there was no evidence of renal failure. These results provide verification of the long-term safety and effectiveness of RSD, even in patients with impaired renal function. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease

PubMed Central

Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

2016-01-01

Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

Acute renal failure after ingestion of guaifenesin and dextromethorphan.

PubMed

Small, Evan; Sandefur, Benjamin J

2014-07-01

Guaifenesin is a common nonprescription medication that has been implicated in drug-induced nephrolithiasis. Dextromethorphan, a nonprescription antitussive found in some guaifenesin-containing preparations, is increasingly recognized as a substance of abuse by many youth and young adults. Renally excreted medications known to have poor solubility in urine have the potential to precipitate when ingested in large quantity, leading to acute obstruction of the ureters and renal failure. We describe the case of a 22-year-old male who developed severe bilateral flank pain, hematuria, and oliguria after an isolated recreational ingestion of guaifenesin and dextromethorphan. The patient was found to have bilateral ureteral obstruction and acute renal failure, suspected to be secondary to precipitation of medication metabolites in the urine. This case highlights the potential for acute renal failure secondary to guaifenesin and dextromethorphan abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

Bardoxolone methyl analogs RTA 405 and dh404 are well tolerated and exhibit efficacy in rodent models of Type 2 diabetes and obesity.

PubMed

Chin, Melanie; Lee, Chun-Yue Ivy; Chuang, Jen-Chieh; Bumeister, Ron; Wigley, W Christian; Sonis, Stephen T; Ward, Keith W; Meyer, Colin

2013-06-15

Bardoxolone methyl and related triterpenoids are well tolerated and efficacious in numerous animal models potentially relevant to patients with Type 2 diabetes and chronic kidney disease. These agents enhance glucose control and regulate lipid accumulation in rodent models of diabetes and obesity, and improve renal function, reduce inflammation, and prevent structural injury in models of renal disease. However, a recent study in Zucker diabetic fatty (ZDF) rats noted poor tolerability with the bardoxolone methyl analog RTA 405 within 1 mo after treatment initiation, although this study was confounded in part by the use of an impure RTA 405 batch. To investigate these discordant observations, the present studies were conducted to further characterize triterpenoids in rodent models of diabetes and obesity. A follow-up study was conducted in ZDF rats with two related triterpenoids (RTA 405 and dh404) for 1.5 mo. Consistent with previous rodent experience, and in contrast to the more recent ZDF report, ZDF rats administered RTA 405 or dh404 exhibited no adverse clinical signs, had laboratory values similar to controls, and exhibited no evidence of adverse liver or kidney histopathology. Additionally, RTA 405 was well tolerated in streptozotocin-induced Type 1 diabetic rats and high-fat-diet-induced obese mice. The present results are consistent with the overall published body of data obtained with triterpenoids and provide further evidence that these molecules are well tolerated without adverse effects on hepatobiliary or renal function in rodent models of diabetes and obesity.

Fluid and electrolyte disturbances in cirrhosis.

PubMed

Papper, S

1976-01-01

Glomerular filtration rate and renal plasma flow may be normal, reduced or increased in cirrhosis. The mechanism of departures from normal is not known. Other renal functional changes in cirrhosis include avid sodium reabsorption, impaired concentrating and diluting abilities, and partial renal tubular acidosis. Fluid and electrolyte disorders are common. Sodium retention with edema and ascites should generally be treated conservatively because they tend to disappear as the liver heals and because forced diuresis has hazards. The indications for diuretics are (1) incipient or overt atelectasis; (2) abdominal distress; and (3) possibility of skin breakdown. Hyponatremia is common and its mechanism and treatment must be assessed in each patient. Hypokalemia occurs and requires treatment. Respiratory alkalosis and renal tubular acidosis seldom need therapy. The hepatorenal syndrome is defined as functional renal failure in the absence of other known causes of renal functional impairment. The prognosis is terrible and therapy is unsatisfactory. The best approach is not to equate the occurrence of renal failure in cirrhosis with the hepatorenal syndrome. Rather the physician should first explore all treatable causes of renal failure, eg, dehydration, obstruction, infection, heart failure, potassium depletion, and others.

[Contribution of X-ray computed tomography in the evaluation of kidney performance].

PubMed

Lemoine, Sandrine; Rognant, Nicolas; Collet-Benzaquen, Diane; Juillard, Laurent

2012-07-01

X-ray computer assisted tomography scanner is an imaging method based on the use of X-ray attenuation in tissue. This attenuation is proportional to the density of the tissue (without or after contrast media injection) in each pixel image of the image. Spiral scanner, the electron beam computed tomography (EBCT) scanner and multidetector computed tomography scanner allow renal anatomical measurements, such as cortical and medullary volume, but also the measurement of renal functional parameters, such as regional renal perfusion, renal blood flow and glomerular filtration rate. These functional parameters are extracted from the modeling of the kinetics of the contrast media concentration in the vascular space and the renal tissue, using two main mathematical models (the gamma variate model and the Patlak model). Renal functional imaging allows measuring quantitative parameters on each kidney separately, in a non-invasive manner, providing significant opportunities in nephrology, both for experimental and clinical studies. However, this method uses contrast media that may alter renal function, thus limiting its use in patients with chronic renal failure. Moreover, the increase irradiation delivered to the patient with multi detector computed tomography (MDCT) should be considered. Copyright © 2011 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Non-invasive evaluation of stable renal allograft function using point shear-wave elastography.

PubMed

Kim, Bom Jun; Kim, Chan Kyo; Park, Jung Jae

2018-01-01

To investigate the feasibility of point shear-wave elastography (SWE) in evaluating patients with stable renal allograft function who underwent protocol biopsies. 95 patients with stable renal allograft function that underwent ultrasound-guided biopsies at predefined time points (10 days or 1 year after transplantation) were enrolled. Ultrasound and point SWE examinations were performed immediately before protocol biopsies. Patients were categorized into two groups: subclinical rejection (SCR) and non-SCR. Tissue elasticity (kPa) on SWE was measured in the cortex of all renal allografts. SCR was pathologically confirmed in 34 patients. Tissue elasticity of the SCR group (31.0 kPa) was significantly greater than that of the non-SCR group (24.5 kPa) (=0.016), while resistive index value did not show a significant difference between the two groups (p = 0.112). Tissue elasticity in renal allografts demonstrated significantly moderate negative correlation with estimated glomerular filtration rate (correlation coefficient = -0.604, p < 0.001). Tissue elasticity was not independent factor for SCR prediction on multivariate analysis. As a non-invasive tool, point SWE appears feasible in distinguishing between patients with SCR and without SCR in stable functioning renal allografts. Moreover, it may demonstrate the functional state of renal allografts. Advances in knowledge: On point SWE, SCR has greater tissue elasticity than non-SCR.

Patient-Related Determinants of Glycaemic Control in People with Type 2 Diabetes in the Gulf Cooperation Council Countries: A Systematic Review.

PubMed

Alramadan, Mohammed J; Afroz, Afsana; Hussain, Sultana Monira; Batais, Mohammed Ali; Almigbal, Turky H; Al-Humrani, Hassan Ahmad; Albaloshi, Ahmed; Romero, Lorena; Magliano, Dianna J; Billah, Baki

2018-01-01

The aim of this systematic review is to assess patient-related factors affecting glycaemic control among people with type 2 diabetes in the Arabian Gulf Council countries. MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL databases were searched from their date of inception to May 2016. Two researchers independently identified eligible studies and assessed the risk of bias. A total of 13 studies met the inclusion criteria. One study was population based, six recruited participants from multiple centres, and the remaining were single centred. The majority of the studies were of low to moderate quality. Factors associated with poor glycaemic control include longer duration of diabetes, low level of education, poor compliance to diet and medication, poor attitude towards the disease, poor self-management behaviour, anxiety, depression, renal impairment, hypertension, and dyslipidaemia. Healthcare providers should be aware of these factors and provide appropriate education and care especially for those who have poor glycaemic control. Innovative educational programs should be implemented in the healthcare systems to improve patient compliance and practices. A variation in the results of the included studies was observed, and some potentially important risk factors such as dietary habits, physical activity, family support, and cognitive function were not adequately addressed. Further research is needed in this area.

Validity of /sup 99m/Tc dimercaptosuccinic acid renal uptake for an assessment for individual kidney function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawamura, J.; Hosakawa, S.; Yoshida, O.

/sup 99m/Tc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a /sup 131/I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. /sup 99m/Tc dimercaptosuccinic acidmore » scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.« less

Assessment of renal injury with a clinical dual head lithotriptor delivering 240 shock waves per minute.

PubMed

Handa, Rajash K; McAteer, James A; Evan, Andrew P; Connors, Bret A; Pishchalnikov, Yuri A; Gao, Sujuan

2009-02-01

Lithotriptors with 2 treatment heads deliver shock waves along separate paths. Firing 1 head and then the other in alternating mode has been suggested as a strategy to treat stones twice as rapidly as with conventional shock wave lithotripsy. Because the shock wave rate is known to have a role in shock wave lithotripsy induced injury, and given that treatment using 2 separate shock wave sources exposes more renal tissue to shock wave energy than treatment with a conventional lithotriptor, we assessed renal trauma in pigs following treatment at rapid rate (240 shock waves per minute and 120 shock waves per minute per head) using a Duet lithotriptor (Direx Medical Systems, Petach Tikva, Israel) fired in alternating mode. Eight adult female pigs (Hardin Farms, Danville, Indiana) each were treated with sham shock wave lithotripsy or 2,400 shock waves delivered in alternating mode (1,200 shock waves per head, 120 shock waves per minute per head and 240 shock waves per minute overall at a power level of 10) to the lower renal pole. Renal functional parameters, including glomerular filtration rate and effective renal plasma flow, were determined before and 1 hour after shock wave lithotripsy. The kidneys were perfusion fixed in situ and the hemorrhagic lesion was quantified as a percent of functional renal volume. Shock wave treatment resulted in no significant change in renal function and the response was similar to the functional response seen in sham shock wave treated animals. In 6 pigs treated with alternating mode the renal lesion was small at a mean +/- SEM of 0.22% +/- 0.09% of functional renal volume. Kidney tissue and function were minimally affected by a clinical dose of shock waves delivered in alternating mode (120 shock waves per minute per head and 240 shock waves per minute overall) with a Duet lithotriptor. These observations decrease concern that dual head lithotripsy at a rapid rate is inherently dangerous.

Renal cell carcinoma, unclassified with medullary phenotype: poorly differentiated adenocarcinomas overlapping with renal medullary carcinoma.

PubMed

Sirohi, Deepika; Smith, Steven C; Ohe, Chisato; Colombo, Piergiuseppe; Divatia, Mukul; Dragoescu, Ema; Rao, Priya; Hirsch, Michelle S; Chen, Ying-Bei; Mehra, Rohit; Amin, Mahul B

2017-09-01

Renal medullary carcinoma (RMC) is a highly aggressive renal cell carcinoma arising in the collecting system and requiring careful correlation with status of sickle cell trait. A panel of international experts has recently proposed provisional diagnostic terminology, renal cell carcinoma, unclassified, with medullary phenotype, based on encountering an extraordinarily rare tumor with RMC morphology and immunophenotype in an individual proven not to have a hemoglobinopathy. Herein, we extend this observation to a cohort of 5 such tumors, morphologically similar to RMC, lacking SMARCB1 expression by immunohistochemistry, but each without evidence of a hemoglobinopathy. The tumors arose in 4 men and 1 woman with a mean age of 44 years, occurring in 3 left and 2 right kidneys. Clinically, aggression was apparent with involvement of perinephric adipose tissue in all 5 cases, nodal metastasis in 4 of 5 cases, and death of disease in 4 of 5 cases within 3-27 months. Histologic sections showed poorly differentiated adenocarcinoma, often with solid and nested growth patterns, as well as infiltrative glandular, tubulopapillary, cribriform, or reticular growth. Rhabdoid and sarcomatoid cytomorphology was seen in a subset. All tumors showed PAX8 nuclear positivity and SMARCB1 loss, with OCT3/4 expression in 4 of 5 cases. In summary, this first series of renal cell carcinoma, unclassified, with medullary phenotype documents tumors with morphologic, immunophenotypic, and prognostic features of RMC occurring in individuals without sickle cell trait. Although greater biologic and molecular understanding is needed, the available evidence points to these cases representing a sporadic counterpart to sickle cell trait-associated RMC. Copyright © 2017 Elsevier Inc. All rights reserved.

Types and Outcome of Fetal Urinary Anomalies in Low Resource Setting Countries: A Retrospective Study.

PubMed

Shalaby, Hend; Hemida, Reda; Nabil, Hanan; Ibrahim, Mohammad

2016-10-01

Congenital anomalies of the kidney and urinary tract in the developing countries have a poor prognosis due to limited experience in antenatal and postnatal management. A 3-year retrospective study was carried out from January 2011 to December 2013. The following data were collected and analyzed: maternal age, gravidity, parity, gestational age at diagnosis, and ultrasonography findings. Final diagnosis after birth, the performed surgeries, follow-up data, as well as survival at one year were also analyzed. The mean age of the included patients was 28 years (range 20-35 years). The mean parity was 1.7 (range 0-4). The mean gestational age at diagnosis was 26 weeks (range 15-36 weeks). Consanguinity was reported in 10 cases (24.4 %). There were 25 males and 16 females. Bilateral renal agenesis was the commonest type (19.5 %). The anomalies of kidneys and urinary tract in our cases were associated with other anomalies in 8 cases (19.5 %). Oligohydramnios was detected in bilateral renal agenesis and posterior urethral valve. Surgical interference during the first 6 months was performed in 6 cases; pyeloplasty for unilateral or bilateral hydronephrosis was performed in 5 cases; and excision of solitary renal cyst performed in one case. By the end of the first year, two of the three cases with chronic renal disease, who were under peritoneal dialysis, died, and three cases who had undergone pyeloplasty were lost to follow-up. Among the 41 cases with antenatally diagnosed renal and urinary malformations; bilateral renal agenesis was the commonest anomaly (19.5 %). There were high rates of induction of abortion, IUFD, and neonatal deaths. The poor outcome may be due to lack of experience in performing invasive therapeutic fetal procedures.

Brentuximab vedotin, an antibody–drug conjugate, in patients with CD30‐positive haematologic malignancies and hepatic or renal impairment

PubMed Central

Chen, Robert; O'Connor, Owen A.; Gopal, Ajay K.; Ramchandren, Radhakrishnan; Goy, Andre; Matous, Jeffrey V.; Fasanmade, Adedigbo A.; Manley, Thomas J.; Han, Tae H.

2016-01-01

Abstract Aims Brentuximab vedotin, an antibody–drug conjugate (ADC), selectively delivers the microtubule‐disrupting agent monomethyl auristatin E (MMAE) into CD30‐expressing cells. The pharmacokinetics of brentuximab vedotin have been characterized in patients with CD30‐positive haematologic malignancies. The primary objective of this phase 1 open label evaluation was to assess the pharmacokinetics of brentuximab vedotin in patients with hepatic or renal impairment. Methods Systemic exposures were evaluated following intravenous administration of 1.2 mg kg–1 brentuximab vedotin in patients with CD30‐positive haematologic malignancies and hepatic (n = 7) or renal (n = 10) impairment and compared with those of unimpaired patients (n = 8) who received 1.2 mg kg–1 brentuximab vedotin in another arm of the study. Results For any hepatic impairment, the ratios of geometric means (90% confidence interval) for AUC(0,∞) were 0.67 (0.48, 0.93) for ADC and 2.29 (1.27, 4.12) for MMAE. Mild or moderate renal impairment caused no apparent change in ADC or MMAE exposures. Severe renal impairment (creatinine clearance <30 ml min–1; n = 3) decreased ADC exposures (0.71 [0.54, 0.94]) and increased MMAE exposures (1.90 [0.85, 4.21]). No consistent pattern of specific adverse events was evident, but analysis of the safety data was confounded by the patients' poor baseline conditions. Five patients died due to adverse events considered unrelated to brentuximab vedotin. All had substantial comorbidities and most had poor baseline performance status. Conclusions Hepatic impairment and severe renal impairment may cause decreases in brentuximab vedotin ADC exposures and increases in MMAE exposures. PMID:27115790

Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study.

PubMed

Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S; Januzzi, James L

2014-01-01

The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153).

Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

PubMed Central

Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K.; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S.; Januzzi, James L.; (GREAT), from the Global Research on Acute Conditions Team

2014-01-01

Objective The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). Methods In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. Results 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. Conclusions In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153). PMID:25386851

Analysis of renal blood flow and renal volume in normal fetuses and in fetuses with a solitary functioning kidney.

PubMed

Hindryckx, An; Raaijmakers, Anke; Levtchenko, Elena; Allegaert, Karel; De Catte, Luc

2017-12-01

To evaluate renal blood flow and renal volume for the prediction of postnatal renal function in fetuses with solitary functioning kidney (SFK). Seventy-four SFK fetuses (unilateral renal agenesis [12], multicystic dysplastic kidney [36], and severe renal dysplasia [26]) were compared with 58 healthy fetuses. Peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the renal artery (RA) were measured; 2D and 3D (VOCAL) volumes were calculated. Renal length and glomerular filtration rate (GFR) were obtained in SFK children (2 years). Compared with the control group, the PSV RA was significantly lower in nonfunctioning kidneys and significantly higher in SFK. Volume measurements indicated a significantly larger volume of SFK compared with healthy kidneys. All but 4 children had GFR above 70 mL/min/1.73 m 2 , and compensatory hypertrophy was present in 69% at 2 years. PSV RA and SFK volume correlated with postnatal renal hypertrophy. No correlation between prenatal and postnatal SFK volume and GFR at 2 years was demonstrated. Low PSV RA might have a predictive value for diagnosing a nonfunctioning kidney in fetuses with a SFK. We demonstrated a higher PSV RA and larger renal volume in the SFK compared with healthy kidneys. © 2017 John Wiley & Sons, Ltd.

Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease.

PubMed

Toth, Peter P; Dwyer, Jamie P; Cannon, Christopher P; Colhoun, Helen M; Rader, Daniel J; Upadhyay, Ashish; Louie, Michael J; Koren, Andrew; Letierce, Alexia; Mandel, Jonas; Banach, Maciej

2018-06-01

Individuals with chronic kidney disease are at increased risk of premature cardiovascular disease. Among them, many with elevated low-density lipoprotein cholesterol (LDL-C) are unable to achieve optimal LDL-C on statins and require additional lipid-lowering therapy. To study this, we compared the LDL-C-lowering efficacy and safety of alirocumab in individuals with hypercholesterolemia with impaired renal function, defined as eGFR 30-59 ml/min/1.73 m 2 , to those without impaired renal function eGFR ≥60 ml/min/1.73 m 2 . A total of 4629 hypercholesterolemic individuals without or with impaired renal function, pooled from eight phase 3 ODYSSEY trials (double-blind treatments of 24-104 weeks), were on alirocumab 150 mg or 75/150 mg every two weeks vs. placebo or ezetimibe. Overall, 10.1% had impaired renal function and over 99% were receiving statin treatment. Baseline LDL-C in alirocumab and control groups was comparable in subgroups analyzed. LDL-C reductions at week 24 ranged from 46.1 to 62.2% or 48.3 to 60.1% with alirocumab among individuals with or without impaired renal function, respectively. Similar reductions were observed for lipoprotein (a), non-high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Safety data were similar in both treatment subgroups, regardless of the degree of CKD. Renal function did not change over time in response to alirocumab. This post hoc efficacy analysis is limited by evaluation of alirocumab treatment effects on renal and lipid parameters by serum biochemistry. Thus, alirocumab consistently lowered LDL-C regardless of impaired renal function, with safety comparable to control, among individuals with hypercholesterolemia who nearly all were on statin treatment. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Case discussion: impaired renal function and tolerance to high altitude.

PubMed

2002-01-01

A 58-year-old woman who plans a trek in the Himalayas at altitudes from 4500 to 5000 m is known to have the loss of about 50% of renal function based on glomerular filtration studies and renal biopsy. Possible risks and management are discussed.

Pre-emptive liver transplantation for primary hyperoxaluria (PH-I) arrests long-term renal function deterioration.

PubMed

Perera, M Thamara P R; Sharif, Khalid; Lloyd, Carla; Foster, Katharine; Hulton, Sally A; Mirza, Darius F; McKiernan, Patrick J

2011-01-01

Primary hyperoxaluria-I (PH-I) is a serious metabolic disease resulting in end-stage renal disease. Pre-emptive liver transplantation (PLT) for PH-I is an option for children with early diagnosis. There is still little information on its effect on long-term renal function in this situation. Long-term assessment of renal function was conducted using Schwartz's formula (estimated glomerular filtration rate-eGFR) in four children (Group A) undergoing PLT between 2002 and 2008, and a comparison was done with eight gender- and sex-matched controls (Group B) having liver transplantation for other indications. All patients received a liver graft from a deceased donor. Median follow-up for the two groups was 64 and 94 months, respectively. One child in Group A underwent re-transplantation due to hepatic artery thrombosis, while acute rejection was seen in one. A significant difference was seen in eGFR at transplant (81 vs 148 mL/min/1.73 m(2)) with greater functional impairment seen in the study population. In Group A, renal function reduced by 21 and 11% compared with 37 and 35% in Group B at 12 and 24 months, respectively. At 2 years post-transplantation, there was no significant difference in eGFR between the two groups (72 vs 100 mL/min/1.73 m(2), respectively; P = 0.06). Renal function remains relatively stable following pre-emptive LTx for PH-I. With early diagnosis of PH-I, isolated liver transplantation may prevent progression to end-stage renal disease and the need for renal transplantation.

A medical oncologist's approach to immunotherapy for advanced renal tumors: is nephrectomy indicated?

PubMed

Cooney, Matthew M; Remick, Scot C; Vogelzang, Nicholas J

2004-02-01

Metastatic renal cell carcinoma is highly resistant to systemic therapy. Although interleukin-2 and interferon remain the most active agents for this disease, long-term survival rates remain poor. Two phase 3 trials, European Organization Research and Treatment of Cancer 30947 and Southwest Oncology Group 8949, have demonstrated a survival benefit of nephrectomy followed by interferon versus interferon alone in patients having an excellent performance status (PS 0 and 1). Removal of the primary tumor followed by interferon is not recommended for patients with a moderate or poor PS (PS 2-4). Even with this aggressive approach, most patients eventually will die from their kidney cancer; therefore, every patient with metastatic disease should be considered for enrollment into clinical trials.

An effective technique to facilitate radiographic stone visualization with an internal stent during shock wave lithotripsy.

PubMed

Sundaram, C P; Saltzman, B

1998-10-01

We describe a simple method to assist stone localization during shock wave lithotripsy in the presence of a Double J stent. A 4F whistle tip ureteral catheter is passed alongside a previously inserted 6F Double J stent. The tip of the ureteral stent is positioned in the lower or mid third of the ureter. Contrast material is injected through the ureteral catheter during lithotripsy to assist stone localization. This technique has been successful in localization of poorly opacified renal stones during lithotripsy. Radiolucent and poorly calcified renal stones can be easily localized during shock wave lithotripsy, despite the presence of a Double J stent. No special catheters or stents are required for this technique.

Renal denervation and hypertension - The need to investigate unintended effects and neural control of the human kidney.

PubMed

Grisk, Olaf

2017-05-01

Increased renal sympathetic nerve activity (RSNA) is present in human and experimental forms of arterial hypertension. Experimental denervation studies showed that renal nerves contribute to the development of hypertension. Clinical trials provided equivocal results on the antihypertensive efficacy of renal denervation in patients spurring discussions on technical aspects of renal denervation and further research on the role of renal nerves for the regulation of kidney function as well as the pathophysiology of hypertension. This review summarizes recent findings on adrenoceptor expression and function in the human kidney, adrenoceptor-dependent regulation of sodium chloride transport in the distal nephron, experimental data on chronic RSNA and the development of high arterial pressure and consequences of renal denervation that may limit its antihypertensive efficacy. Future research needs to reduce the gap between our knowledge on neural control of renal function in animals vs. humans to facilitate translation of experimental animal data to humans. More experimental studies on the temporal relationship between RSNA and arterial pressure in the chronic setting are needed to better define the pathogenetic role of heightened RSNA in different forms of arterial hypertension in order to improve the rational basis for renal denervation in antihypertensive therapy. Finally, research on unintended consequences of renal denervation including but not limited to reinnervation and denervation supersensitivity needs to be intensified to further assess the potential of renal denervation to slow the progression of renal disease and hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

[Pleural metastases of renal carcinoma].

PubMed

Giigoruk, O G; Lazarev, A F; Doroshenko, V S

2007-01-01

Metastases in renal carcinoma are diagnosed at initial diagnosis in 25% examinees. Traditional renal carcinoma has higher metastatic potential, is associated with worse survival of the patients compared to papillary cancer. We studied cytological characteristics of renal carcinoma metastases to the pleura in comparison with histological studies of the primary lesion using immunohistochemical findings. We examined cytologically pleural liquid in renal carcinoma metastases to the pleura in 6 patients (2.3% of carcinomatous pleuricies). High efficacy was shown by a cytocentrifuge CYTOSPIN-4. In 3 cases initial cancer was renal cell carcinoma, pleural exudation developed 2 years later, clear cell carcinoma appeared 6 years later and papillary cancer--10 years later. In the other 3 cases malignant cells were detected in new-onset cases. Renal carcinoma was diagnosed in one case. Cytological preparations were studied with identification of cytological signs typical for classic clear cell, granulocell and papillary renal cancer. Immunohistochemical examination of primary tumor lesion in the kidney discovered high proliferative activity of tumor cells by Ki-67 index to 5.28%. The tumors had solitary Bcl-2 positive cells. Expression of mutant p-53 took place in 0.93%. Her-2/neu hyperexpression was not found in the tumors of the above patients. Such immunohistochemical parameters point to poor prognosis. This is confirmed by renal carcinoma metastases to the pleura.

Fully automatic region of interest selection in glomerular filtration rate estimation from 99mTc-DTPA renogram.

PubMed

Lin, Kun-Ju; Huang, Jia-Yann; Chen, Yung-Sheng

2011-12-01

Glomerular filtration rate (GFR) is a common accepted standard estimation of renal function. Gamma camera-based methods for estimating renal uptake of (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) without blood or urine sampling have been widely used. Of these, the method introduced by Gates has been the most common method. Currently, most of gamma cameras are equipped with a commercial program for GFR determination, a semi-quantitative analysis by manually drawing region of interest (ROI) over each kidney. Then, the GFR value can be computed from the scintigraphic determination of (99m)Tc-DTPA uptake within the kidney automatically. Delineating the kidney area is difficult when applying a fixed threshold value. Moreover, hand-drawn ROIs are tedious, time consuming, and dependent highly on operator skill. Thus, we developed a fully automatic renal ROI estimation system based on the temporal changes in intensity counts, intensity-pair distribution image contrast enhancement method, adaptive thresholding, and morphological operations that can locate the kidney area and obtain the GFR value from a (99m)Tc-DTPA renogram. To evaluate the performance of the proposed approach, 30 clinical dynamic renograms were introduced. The fully automatic approach failed in one patient with very poor renal function. Four patients had a unilateral kidney, and the others had bilateral kidneys. The automatic contours from the remaining 54 kidneys were compared with the contours of manual drawing. The 54 kidneys were included for area error and boundary error analyses. There was high correlation between two physicians' manual contours and the contours obtained by our approach. For area error analysis, the mean true positive area overlap is 91%, the mean false negative is 13.4%, and the mean false positive is 9.3%. The boundary error is 1.6 pixels. The GFR calculated using this automatic computer-aided approach is reproducible and may be applied to help nuclear medicine physicians in clinical practice.

Clinical characteristics and one-year mortality according to admission renal function in patients with a first acute heart failure hospitalization.

PubMed

Formiga, Francesc; Moreno-Gonzalez, Rafael; Chivite, David; Casado, Jesús; Escrihuela-Vidal, Francesc; Corbella, Xavier

2018-02-01

Chronic kidney disease is related to poor outcomes in patients with heart failure (HF). Few studies have assessed whether renal function influences one-year mortality risk in patients admitted for the first time for acute HF. We reviewed the medical records of all patients aged >50 years admitted within a two-year period for a first episode of decompensated HF. The sample was divided according to the patients' estimated glomerular filtration rate (eGFR) on admission into three groups (eGFR >60, 30-60 and <30 ml/min/1.73 m 2 ). Index admission and one-year all-cause mortality rates were compared between groups using Cox regression analysis. A total of 985 patients were included in the study, mean age 78.4±9 years, and with mean admission eGFR of 60.5±26 ml/min/1.73 m 2 . Of these, 516 (52.3%) patients had eGFR <60 ml/min/1.73 m 2 . One-year all-cause mortality was 25.4%, with a significant association between worse eGFR category and mortality (p<0.0001). Cox regression analysis assessing eGFR as a categorical variable confirmed this association (HR 1.378; p=0.030), together with older age (HR 1.066; p<0.001), previous diagnosis of hypertension (HR 0.527; p<0.001), and both lower systolic blood pressure (HR 0.993; p=0.009) and higher serum potassium on admission (HR 1.471; p <0.001). Renal impairment is common in HF patients, even at the time of first admission. In this group of HF patients the presence of renal impairment was associated with higher mid-term (one-year) mortality risk. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Renal Salvage with Renal Artery Stenting Improves Long-term Survival.

PubMed

Modrall, J Gregory; Trimmer, Clayton; Tsai, Shirling; Kirkwood, Melissa L; Ali, Mujtaba; Rectenwald, John E; Timaran, Carlos H; Rosero, Eric B

2017-11-01

The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) Trial cast doubt on the benefits of renal artery stenting (RAS). However, the outcomes for patients with chronic kidney disease (CKD) were not analyzed separately in the CORAL Trial. We hypothesized that patients who experienced a significant improvement in renal function after RAS would have improved long-term survival, compared with patients whose renal function was not improved by stenting. This single-center retrospective study included 60 patients with stage 3 or worse CKD and renal artery occlusive disease who were treated with RAS for renal salvage. Patients were categorized as "responders" or "nonresponders" based on postoperative changes in estimated glomerular filtration rate (eGFR) after RAS. "Responders" were those patients with an improvement of at least 20% in eGFR over baseline; all others were categorized as "nonresponders." Survival was analyzed using the Kaplan-Meier method. Cox proportional hazards regression was used to identify predictors of long-term survival. The median age of the cohort was 66 years (interquartile range [IQR], 60-73). Median preoperative eGFR was 34 mL/min/1.73 m 2 (IQR, 24-45). At late follow-up (median 35 months, IQR, 22-97 months), 16 of 60 patients (26.7%) were categorized as "responders" with a median increase in postoperative eGFR of 40% (IQR, 21-67). Long-term survival was superior for responders, compared with nonresponders (P = 0.046 by log-rank test). Cox proportional hazards regression identified improved renal function after RAS as the only significant predictor of increased long-term survival (hazard ratio = 0.235, 95% confidence interval = 0.075-0.733; P = 0.0126 for improved versus worsened renal function after RAS). Successful salvage of renal function by RAS is associated with improved long-term survival. These data provide an important counter argument to the prior negative clinical trials that found no benefit to RAS. Published by Elsevier Inc.

Peripheral and central interactions between the renin-angiotensin system and the renal sympathetic nerves in control of renal function.

PubMed

DiBona, G F

2001-06-01

Increases in renal sympathetic nerve activity (RSNA) regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. As increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between RSNA and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, that is, the direct (via specific innervation) and indirect (via angiotensin II) contributions of increased RSNA to the regulation of renal function. The effects of increased RSNA on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with angiotensin-converting enzyme inhibitors or angiotensin II-type AT1 receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated following renal denervation. These interactions can also be extrarenal, that is, in the central nervous system, wherein RSNA and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, the permeable blood-brain barrier of which permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II type AT1 receptor antagonists, into the ventricular system or microinjected into the rostral ventrolateral medulla, are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (e.g., congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and RSNA are involved in influencing the neural control of renal function.

Effects of short-term addition of NSAID to diuretics and/or RAAS-inhibitors on blood pressure and renal function.

PubMed

Nygård, Peder; Jansman, Frank G A; Kruik-Kollöffel, Willemien J; Barnaart, Alex F W; Brouwers, Jacobus R B J

2012-06-01

The combined post-operative use of diuretics and/or renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of nonsteroidal anti-inflammatory drug (NSAID) associated renal failure because of a drug-drug interaction. The aim of this study was to investigate the effect of the short-term (<4 days) post-operative combined use of NSAIDs with diuretics and/or RAAS inhibitors on renal function and blood pressure. One teaching hospital in the Netherlands. The study-design was a prospective, observational cohort-study. Based on postoperative treatment with NSAIDs, the intervention-group was compared to a control-group (no NSAIDs treatment). Systolic blood pressure and renal function expressed by the estimated glomular filtration rate (eGFR) calculated with the modification of renal desease formula. 97 patients were included in the intervention-group, 53 patients in the control-group. Patient characteristics were comparable except for one variable: 'combined use of a diuretic with a RAAS inhibitor' which was higher in the control-group (62 vs. 43 %, p = 0.046). Odds ratio for clinically relevant increase in systolic blood pressure was 0.66 (CI95 % 0.3-1.5). Odds ratio for clinical relevant decrease in renal function was 2.44 (CI95 % 1.1-5.2). On day 4 eGFR of 3 patients in the intervention- and 1 in the control-group was <50 ml/min/1.73 m(2). Odds ratios showed no significant difference of a clinically relevant increase in systolic blood pressure but showed a higher risk for a clinically relevant decrease in renal function in the intervention group. However this decrease resulted in a relevant impaired renal function (<50 ml/min/1.73 m(2)) in only 3 patients in the interventiongroup and 1 patient in the control-group. In the post-operative patient, without preexisting impaired renal function, concurrent diuretics and/or renin-angiotensinaldosterone system inhibitor therapy can be combined with short-term NSAID treatment.

[Kidney function and liver transplantation].

PubMed

Gámán, György; Gelley, Fanni; Gerlei, Zsuzsa; Dabasi, Eszter; Görög, Dénes; Fehérvári, Imre; Kóbori, László; Lengyel, Gabriella; Zádori, Gergely; Fazakas, János; Doros, Attila; Sárváry, Enikő; Nemes, Balázs

2013-06-30

In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. Retrospective data analysis was performed after primary liver transplantations (n = 319). impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). Selection of personalized immunosuppressive medication has a positive effect on renal function.

Catheter-Based Radiorefrequency Renal Denervation Lowers Blood Pressure in Obese Hypertensive Dogs

PubMed Central

Henegar, Jeffrey R.; Zhang, Yongxing; Rama, Rita De; Hata, Cary; Hall, Michael E.

2014-01-01

BACKGROUND Obesity-induced hypertension appears to be due, in part, to increased renal sympathetic activity. Catheter-based renal denervation (RD) has been reported to lower arterial blood pressure (BP) in humans with resistant hypertension, many of whom are obese. This study was performed to assess the impact of radiofrequency–induced RD on renal function, BP, renal norepinephrine (NE), and histology of nerves along the renal artery in obese, hypertensive dogs, an experimental model that closely mimics cardiorenal and metabolic changes in obese hypertensive humans. METHODS After control measurements of cardiovascular and renal function were obtained in obese dogs fed a high-fat diet, bilateral RD was performed using the St. Jude Medical EnligHTN RD system. After RD, BP was measured continuously for 8 weeks, and glomerular filtration rate (GFR) was measured biweekly for 6 weeks. At the end of the study, renal arteries were collected for histological analysis, and kidneys were obtained for NE measurement. RESULTS Eight weeks after RD, systolic BP fell from 157±5mm Hg pre-RD to 133±3mm Hg (P < 0.01), and mean arterial pressure decreased by 9mm Hg compared with pre-RD (P < 0.01). There were no significant changes in GFR. Renal nerve injury was most prevalent 0.28–3.5mm from the renal artery lumen. RD caused injury in 46% of the renal nerves observed and reduced renal tissue NE by 42% (P < 0.01). CONCLUSIONS Catheter-based RD with the St. Jude Medical EnligHTN system lowers BP in obese dogs without significantly compromising renal function. PMID:24709437

Effects of PEG-PLA-nano Artificial Cells Containing Hemoglobin on Kidney Function and Renal Histology in Rats

PubMed Central

Liu, Zun Chang; Chang, Thomas M.S.

2012-01-01

This study is to investigate the long-term effects of PEG-PLA nano artificial cells containing hemoglobin (NanoRBC) on renal function and renal histology after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: NanoRBC in Ringer lactate, Ringer lactate, stroma-free hemoglobin (SFHB), polyhemoglobin (PolyHb), autologous rat whole blood (rat RBC). Blood samples were taken before infusions and on days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on day 21 after infusions and kidneys were excised for histology examination. Infusion of SFHB induced significant decrease in renal function damage evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed damaged. In all the other groups, NanoRBC, PolyHb, Ringer lactate and rat RBC, there were no abnormalities in renal biochemistry or histology. In conclusion, injection of NanoRBC did not have adverse effects on renal function nor renal histology. PMID:18979292

Utility of Cystatin C to monitor renal function in Duchenne muscular dystrophy

PubMed Central

Viollet, Laurence; Gailey, Susan; Thornton, David J.; Friedman, Neil R.; Flanigan, Kevin M.; Mahan, John D.; Mendell, Jerry R.

2009-01-01

Introduction: Creatinine as a marker of renal function has limited value in Duchenne muscular dystrophy (DMD) because of reduced muscle mass. Alternative methods of assessing renal function are sorely needed. Cystatin C, a nonglycosylated protein unaffected by muscle mass, is potentially an ideal biomarker of nephrotoxicity for this population but requires validation. Methods: 75 subjects were recruited: 35 DMD (mean age 10.8 ± 5.4 years, corticosteroids n = 19, ambulatory n = 26), 29 healthy controls, 10 with renal disease, and one DMD with renal failure. Results: Cystatin C levels in DMD were normal irrespective of age, ambulation or corticosteroid treatment. Serum cystatin C was 0.67 ± 0.11 mg/L compared to normal controls 0.69 ± 0.09. mg/L. In these same individuals serum creatinine was severely reduced (0.27 ± 0.12 mg/dL) versus normals (0.75 ± 0.15 mg/dL, p < 0.01). In one DMD subject in renal failure, cystatin C was elevated. Discussion: This study demonstrates the potential value of cystatin C as a biomarker for monitoring renal function in DMD. Its applicability extends to other neuromuscular diseases. PMID:19623638

Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

PubMed

Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

2011-01-01

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

Can renal dysfunction after infra-renal aortic aneurysm repair be modified by multi-antioxidant supplementation?

PubMed

Wijnen, M H W A; Vader, H L; Van Den Wall Bake, A W L; Roumen, R M H

2002-08-01

Renal failure after lower torso ischemia is a serious problem, partly caused by hypotension and indirect reperfusion injury. This injury is partly due to the formation of oxygen free radicals by activated neutrophils. This injury results in albuminuria and renal function impairment. There are indications that free radical damage in indirect reperfusion injury can be diminished by administering extra antioxidants before and during reperfusion. In this prospective randomised study we have looked at the influence of a multi-antioxidant supplementation on renal function in patients undergoing an elective open infrarenal abdominal aneurysm repair. The patients received either standard treatment (n=22) or standard treatment with additional antioxidants perioperatively (Allopurinol, vitamin E and C, N-acetylcysteine and mannitol). For renal function we have looked at the albumin/creatinine ratio in urine and 24 hr creatinine clearance. Despite significantly increased serum total antioxidant capacity, the group receiving extra antioxidants showed no decrease in the albumin/creatinine ratio in urine. There was however a significantly higher creatinine clearance in this group at day 2. The results indicate that the diminished renal function after infrarenal aneurysm repair may be influenced by antioxidant therapy.

Using OCT to predict post-transplant renal function

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Chen, Yu; Wierwille, Jeremiah; Joh, Daniel; Alexandrov, Peter; Rogalsky, Derek; Moody, Patrick; Chen, Allen; Cooper, Matthew; Verbesey, Jennifer E.; Gong, Wei; Wang, Hsing-Wen

2013-03-01

The treatment of choice for patients with end-stage renal disease is kidney transplantation. However, acute tubular necrosis (ATN) induced by an ischemic insult (e.g., from prolonged ex vivo storage times, or non-heart beating cadavers) is a major factor limiting the availability of donor kidneys. In addition, ischemic induced ATN is a significant risk factor for eventual graft survival and can be difficult to discern from rejection. Currently, there are no rapid and reliable tests to determine ATN suffered by donor kidneys and whether or not donor kidneys might exhibit delayed graft function. OCT (optical coherence tomography) is a rapidly emerging imaging modality that can function as a type of "optical biopsy", providing cross-sectional images of tissue morphology in situ and in real-time. In a series of recent clinical trials, we evaluated the ability of OCT to image those features of the renal microstructure that are predictive of ATN. Specifically, we found that OCT could effectively image through the intact human renal capsule and determine the extent of acute tubular necrosis. We also found that Doppler based OCT (i.e., DOCT) revealed renal blood flow dynamics that is also reported to be a determiner of post-transplant renal function. This kind of information will allow transplant surgeons to make the most efficient use of available donor kidneys, eliminate the possible use of bad donor kidneys, provide a measure of expected post-transplant renal function, and allow better distinction between post-transplant immunological rejection and ischemic-induced acute renal failure.

A Single-Dose, Open-Label Study of the Pharmacokinetics, Safety, and Tolerability of Lisdexamfetamine Dimesylate in Individuals With Normal and Impaired Renal Function

PubMed Central

Ermer, James; Corcoran, Mary; Lasseter, Kenneth; Marbury, Thomas; Yan, Brian

2016-01-01

Background: Lisdexamfetamine (LDX) and d-amphetamine pharmacokinetics were assessed in individuals with normal and impaired renal function after a single LDX dose; LDX and d-amphetamine dialyzability was also examined. Methods: Adults (N = 40; 8/group) were enrolled in 1 of 5 renal function groups [normal function, mild impairment, moderate impairment, severe impairment/end-stage renal disease (ESRD) not requiring hemodialysis, and ESRD requiring hemodialysis] as estimated by glomerular filtration rate (GFR). Participants with normal and mild to severe renal impairment received 30 mg LDX; blood samples were collected predose and serially for 96 hours. Participants with ESRD requiring hemodialysis received 30 mg LDX predialysis and postdialysis separated by a washout period of 7–14 days. Predialysis blood samples were collected predose, serially for 72 hours, and from the dialyzer during hemodialysis; postdialysis blood samples were collected predose and serially for 48 hours. Pharmacokinetic end points included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from time 0 to infinity (AUC0–∞) or to last assessment (AUClast). Results: Mean LDX Cmax, AUClast, and AUC0–∞ in participants with mild to severe renal impairment did not differ from those with normal renal function; participants with ESRD had higher mean Cmax and AUClast than those with normal renal function. d-amphetamine exposure (AUClast and AUC0–∞) increased and Cmax decreased as renal impairment increased. Almost no LDX and little d-amphetamine were recovered in the dialyzate. Conclusions: There seems to be prolonged d-amphetamine exposure after 30 mg LDX as renal impairment increases. In individuals with severe renal impairment (GFR: 15 ≤ 30 mL·min−1·1.73 m−2), the maximum LDX dose is 50 mg/d; in patients with ESRD (GFR: <15 mL·min−1·1.73 m−2), the maximum LDX dose is 30 mg/d. Neither LDX nor d-amphetamine is dialyzable. PMID:26926668

Delafloxacin Pharmacokinetics in Subjects With Varying Degrees of Renal Function

PubMed Central

Hoover, Randall K.; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K.; Quintas, Megan

2017-01-01

Abstract Delafloxacin, a fluoroquinolone, has activity against gram‐positive organisms including methicillin‐resistant Staphylococcus aureus and fluoroquinolone‐susceptible and –resistant gram‐negative organisms. This study was conducted to determine delafloxacin pharmacokinetics after a single intravenous infusion or oral dose administration in subjects with varying degrees of renal function. The study was an open‐label, parallel‐group crossover study in subjects with normal renal function or with mild, moderate, or severe renal impairment. Subjects received 300 mg delafloxacin intravenously, placebo intravenously, and 400 mg delafloxacin orally in 3 periods separated by ≥14‐day washouts. Blood and urine pharmacokinetic parameters were calculated using noncompartmental methods. Delafloxacin total clearance decreased with decreasing renal function, with a corresponding increase in AUC0–∞. After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC0–∞ was 22.6 and 45.0 μg·h/mL in normal and severe renal subjects, respectively. Mean renal clearance as determined by urinary excretion was 6.03 and 0.44 L/h in normal and severe renal impairment subjects, respectively. Total clearance exhibited linear relationships to eGFR and CLCR. Similar observations were found after oral administration of delafloxacin. Single doses of delafloxacin 300 mg intravenously and 400 mg orally were well tolerated in all groups. In conclusion, renal insufficiency has an effect on delafloxacin clearance; a dosing adjustment for intravenous dosing is warranted for patients with severe renal impairment (eGFR < 30 mL/min). PMID:29251785

Differentiation of vasoactive renal sympathetic nerve fibres.

PubMed

Dibona, G F

2000-01-01

Activation of renal sympathetic nerves produces marked changes in renal haemodynamics, tubular ion and water transport and renin secretion. This review examines information indicating that these effects are mediated by functionally specific groups of renal sympathetic nerve fibres separately innervating the renal vessels, tubules and juxtaglomerular granular cells.

Predictors of dietary and fluid non-adherence in Jordanian patients with end-stage renal disease receiving haemodialysis: a cross-sectional study.

PubMed

Khalil, Amani A; Darawad, Muhammad; Al Gamal, Eklas; Hamdan-Mansour, Ayman M; Abed, Mona A

2013-01-01

The purpose of this study is to provide insight into the relationship between dietary and fluid non-adherence, depressive symptoms, quality of life, perceived barriers and benefits of exercise, and perceived social support among Jordanian patients with end-stage renal disease receiving haemodialysis using Pender's health promotion model. Non-adherence to dietary and fluid restrictions is a leading cause of treatment failure and poor outcomes in end-stage renal disease. Yet, factors that interfere with the patients' ability to follow their dietary restrictions are unknown. A descriptive, correlational, cross-sectional design was used. Jordanian patients (n = 190) with end-stage renal disease receiving haemodialysis from three main Jordanian cities were included. The dialysis diet and fluid nonadherence questionnaire, Beck Depression Inventory-II, Quality Of Life Index, Dialysis Patient-Perceived Exercise Benefits and Barriers Scale, and the Multidimensional Perceived Social Support were employed to measure the key variables. Patients were more likely men with mean age of 48·2 ± 14·9. Only 27% of the patients showed full commitment to diet guidelines and 23% to fluid guidelines during the last 14 days. Depression (M = 18·8 ± 11·4) had significant negative association with quality of life (importance and satisfaction) (r = -0·60, r = -0·32, p = 0·001, respectively). Multiple hierarchal regressions revealed a predictive model of only two variables: age (B = -0·22, p = 0·05) and residual renal function (B = -0·23, p = 0·012) for dietary non-adherence. Non-adherence to diet and fluid guidelines association with individual characteristics, health perception and psychosocial variables should be investigated in a longitudinal design. Relationship of non-adherence with culture-related factors should deeply be assessed among Jordanian patients with end-stage renal disease receiving haemodialysis. Identification of the factors that may worsen dietary and fluid non-adherence may lead to improved therapeutic interventions within the mainstream of medical practice for Jordanian patients with end-stage renal disease receiving haemodialysis. © 2012 Blackwell Publishing Ltd.

Renal impairment in HIV-infected patients initiating tenofovir-containing antiretroviral therapy regimens in a Primary Healthcare Setting in South Africa.

PubMed

Kamkuemah, Monika; Kaplan, Richard; Bekker, Linda-Gail; Little, Francesca; Myer, Landon

2015-04-01

Long-term use of tenofovir disoproxil fumarate is associated with declines in glomerular function and chronic kidney disease in HIV-infected patients. We aimed to assess the prevalence and incidence of renal impairment in a primary care setting in sub-Saharan Africa. We analysed data from 1092 HIV-infected patients initiating tenofovir at a primary care clinic in Cape Town, South Africa. Renal function was assessed for the first 12 months on ART by estimating glomerular filtration rate (eGFR) calculated using the Cockroft-Gault equation categorised into normal, mild, moderate and severe reduction in renal function based on values >90, 60-89, 30-59 and <30 ml/min/1.73 m(2) , respectively. Associations were assessed using logistic regression, and average GFR trajectory over time was modelled using linear mixed-effects models. The cohort consisted of 62% women; median age was 34 years (IQR 29; 41 years). The majority had normal renal function pre-ART (79%), 19% had mildly reduced GFR, and 2% had moderate renal impairment. Older age, more advanced WHO stage and anaemia were independently associated with prevalent renal impairment. On average, estimated glomerular function improved over the first year on tenofovir [1.10 ml/min/1.73 m(2) average increase over 12 months (95% CI: 0.80; 1.40)]. Male gender, anaemia and immunosuppression (WHO Stage III/IV and CD4 cell counts <100 cells/mm(3) ) were associated with lower average eGFR levels over time. Overall, 3% developed eGFR <50 ml/min/1.73 m(2) during this period. Serum creatinine tests conducted before 4 months on ART had low predictive value for predicting change in eGFR after a year on ART. Generally, renal function improved in HIV-infected adults initiating ART in this primary healthcare setting during the first year on ART. While monitoring of renal function is recommended in the first 4 months on ART, renal impairment appears uncommon during the first 12 months of tenofovir-containing ART in primary care populations. © 2014 John Wiley & Sons Ltd.

Cystatin C a marker for renal function after exercise.

PubMed

Mingels, A; Jacobs, L; Kleijnen, V; Wodzig, W; Dieijen-Visser, M van

2009-09-01

Renal impairment is common during and after severe exercise. In clinical practice, renal function is evaluated using serum creatinine, urine parameters, and equations to estimate the Glomular Filtration Rate (GFR). However, creatinine levels may be biased by skeletal muscle damage and the GFR equations, requiring age, gender and body weight, are shown to be inadequate in normals. In the present study, we show that serum cystatin C and creatinine concentrations were elevated after marathon running in 26% and 46% of the 70 recreational male runners, respectively, possibly because of reduction in renal blood flow. The mean cystatin C increase was twice as low as compared to creatinine (21% and 41%, respectively), suggesting that cystatin C is indeed less biased by muscle damage. Future research has to reveal whether training diminishes the elevation in renal markers. Overall, cystatin C seems a more reliable method to establish renal function during and after extensive exercise. Georg Thieme Verlag KG Stuttgart.

[Methodological aspects related to the determination of the relative renal function using 99mTC MAG3].

PubMed

Ladrón De Guevara Hernández, D; Ham, H; Franken, P; Piepsz, A; Lobo Sotomayor, G

2002-01-01

The aim of the study was to evaluate three different methods for calculating the split renal function in patients with only one functioning kidney, keeping in mind that the split function should be zero on the side of the non-functioning kidney. We retrospectively selected 28 99mTc MAG3 renograms performed in children, 12 with unilateral nephrectomy, 4 with unilateral agenesis and 12 with a non-functioning kidney. A renal and perirenal region of interest (ROI) were delineated around the functioning kidney. The ROIs around the empty kidney were drawn symmetrically to the contralateral side. The split renal function was calculated using three different methods, the integral method, the slope method and the Patlak-Rutland algorithm. For the whole group of 28 kidneys as well as for the three categories of patients, the three methods provided a split function on the side of the non-functioning kidney close to the zero value, regardless of whether the empty kidney was the left or the right one. We recommend the use of the integral method for the whole range of split renal function with 99mTc MAG3. No significant improvement was obtained by means of the more sophisticated Patlak-Rutland method.

Renal impairment in stroke patients: A comparison between the haemorrhagic and ischemic variants.

PubMed

Shrestha, Pratyush; Thapa, Shalima; Shrestha, Shikher; Lohani, Subash; Bk, Suresh; MacCormac, Oscar; Thapa, Lekhjung; Devkota, Upendra Prasad

2017-01-01

Background: Renal impairment is regularly seen in hospitalized stroke patients, affecting the outcome of patients, as well as causing difficulties in their management. A prospective cohort study was conducted to assess the trend of renal function in hospitalized ischemic and haemorrhagic stroke patients. The incidence of renal impairment in these subgroups, the contributing factors and the need for renal replacement in renal impaired patients was evaluated. Methods: Alternate day renal function testing was performed in hospitalized stroke patients. Estimated glomerular filtration rate (e-GFR) was calculated and the trend of renal function in the two stroke subgroups (haemorrhagic and ischemic) was assessed, with renal impairment defined as e-GFR < 60mL/ minute per 1.73m 2 . Results: Among 52 patients, 25 had haemorrhagic stroke (mean age 59.81 ± 14.67) and 27 had ischemic stroke (mean age 56.12 ± 13.08). The mean e-GFR (mL/minute per 1.732m 2 ) at admission in the haemorrhagic stroke subgroup was 64.79 ± 25.85 compared to 86.04 ± 26.09 in the ischemic stroke subgroup (p=0.005). Sixteen out of 25 (64%) patients in the haemorrhagic stroke subgroup and 9 out of 27 (33.3%) patients in the ischemic subgroup developed renal impairment (p=0.027). The location of the bleed (p=0.8), volume of hematoma (p=0.966) and surgical intervention (p=0.4) did not predispose the patients to renal impairment. One out of 16 patients with haemorrhagic stroke (who eventually died), and 2 out of 9 patients with ischemic stroke required renal replacement. Conclusion : Renal impairment is commonly seen in stroke patients, more so in patients who suffered haemorrhagic strokes.  The impairment, however, is transient and rarely requires renal replacement therapy.

Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function.

PubMed

Cawello, Willi; Ahrweiler, Sascha; Sulowicz, Wladyslaw; Szymczakiewicz-Multanowska, Agnieszka; Braun, Marina

2012-01-01

To evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis). METHODS All subjects received a single transdermal 10 cm² patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h⁻¹). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites. Point estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,t(last) ) and C(max) for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for C(max) for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency. The pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis. © 2011 UCB Biosciences GmbH. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Single dose pharmacokinetics of the transdermal rotigotine patch in patients with impaired renal function

PubMed Central

Cawello, Willi; Ahrweiler, Sascha; Sulowicz, Wladyslaw; Szymczakiewicz-Multanowska, Agnieszka; Braun, Marina

2012-01-01

AIM To evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis). METHODS All subjects received a single transdermal 10 cm2 patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h−1). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites. RESULTS Point estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,tlast) and Cmax for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for Cmax for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency. CONCLUSIONS The pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis. PMID:21707699

Problems Associated With Access to Renal Replacement Therapy: Experience of the Sindh Institute of Urology and Transplantation.

PubMed

Mazhar, Farida; Nizam, Naveeda; Fatima, Nazia; Siraj, Sana; Rizvi, Syed Adibul Hasan

2017-02-01

The prevalence of end-stage renal disease is increasing worldwide. It is also one of the main health problems in Pakistan. Currently, hemodialysis represents the main mode of treatment for patients with end-stage renal disease in this country. Despite 24-hour free dialysis at the Sindh Institute of Urology and Transplantation (Karachi, Pakistan), a significant number of patients do not turn up for regular dialysis or miss regular sessions of dialysis. We conducted this study to identify and highlight the factors leading to poor compliance with regular hemodialysis treatment despite free dialysis treatment offered at our center. In 2014, 4565 patients with end-stage renal disease were registered at the Sindh Institute of Urology and Transplantation. Among these, 610 patients (13.4%) missed more than 2 sessions of dialysis and were included in the present study. Patients provided written informed consent before study participation. Data were collected from a questionnaire survey and analyzed by SPSS software (SPSS: An IBM Company, version 20.0, Chicago, IL, USA). Despite 24-hour dialysis facilities, the patient drop-out rate (779; 18%) was high. In addition, a significant minority of patients (610; 13.4%) was erratic in adherence to maintenance hemodialysis schedules, with > 2 missed appointments. The mean age of these 610 patients was 33.4 ± 7.4 years, and 345 patients (57%) were males. The main factors leading to poor compliance included cost of travel (33.2%), lack of affordable lodging and boarding facilities near dialysis center (30.9%), long distances from dialysis center (20.1%), and lack of family support (15.6%). This study shows that there is significant drop-out and poor compliance rates for regular dialysis despite free dialysis facilities.

Screening for Albuminuria Identifies Individuals at Increased Renal Risk

PubMed Central

van der Velde, Marije; Halbesma, Nynke; de Charro, Frank T.; Bakker, Stephan J.L.; de Zeeuw, Dick; de Jong, Paul E.; Gansevoort, Ronald T.

2009-01-01

It is unknown whether screening for albuminuria in the general population identifies individuals at increased risk for renal replacement therapy (RRT) or accelerated loss of renal function. Here, in a general population-based cohort of 40,854 individuals aged 28 to 75 yr, we collected a first morning void for measurement of urinary albumin. In a subset of 6879 individuals, we measured 24-h urinary albumin excretion and estimated GFR at baseline and during 6 yr of follow-up. Linkage with the national RRT registry identified 45 individuals who started RRT during 9 yr of follow-up. The quantity of albuminuria was associated with increased renal risk: the higher the level of albuminuria, the higher the risk of need for renal replacement therapy and the more rapid renal function decline. A urinary albumin concentration of ≥20 mg/L identified individuals who started RRT during follow-up with 58% sensitivity and 92% specificity. Of the identified individuals, 39% were previously unknown to have impaired renal function, and 50% were not being medically treated. Restricting screening to high-risk groups (e.g., known hypertension, diabetes, cardiovascular disease [CVD], older age) reduced the sensitivity of the test only marginally but failed to identify 45% of individuals with micro- and macroalbuminuria. In conclusion, individuals with elevated levels of urinary albumin are at increased risk for RRT and accelerated loss of renal function. Screening for albuminuria identifies patients at increased risk for progressive renal disease, 40 to 50% of whom were previously undiagnosed or untreated. PMID:19211710

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

PubMed

Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2018-06-01

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

Regulation of Polycystin-1 Function by Calmodulin Binding

PubMed Central

Doerr, Nicholas; Wang, Yidi; Kipp, Kevin R.; Liu, Guangyi; Benza, Jesse J.; Pletnev, Vladimir; Pavlov, Tengis S.; Staruschenko, Alexander; Mohieldin, Ashraf M.; Takahashi, Maki; Nauli, Surya M.; Weimbs, Thomas

2016-01-01

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common genetic disease that leads to progressive renal cyst growth and loss of renal function, and is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The PC1/PC2 complex localizes to primary cilia and can act as a flow-dependent calcium channel in addition to numerous other signaling functions. The exact functions of the polycystins, their regulation and the purpose of the PC1/PC2 channel are still poorly understood. PC1 is an integral membrane protein with a large extracytoplasmic N-terminal domain and a short, ~200 amino acid C-terminal cytoplasmic tail. Most proteins that interact with PC1 have been found to bind via the cytoplasmic tail. Here we report that the PC1 tail has homology to the regulatory domain of myosin heavy chain including a conserved calmodulin-binding motif. This motif binds to CaM in a calcium-dependent manner. Disruption of the CaM-binding motif in PC1 does not affect PC2 binding, cilia targeting, or signaling via heterotrimeric G-proteins or STAT3. However, disruption of CaM binding inhibits the PC1/PC2 calcium channel activity and the flow-dependent calcium response in kidney epithelial cells. Furthermore, expression of CaM-binding mutant PC1 disrupts cellular energy metabolism. These results suggest that critical functions of PC1 are regulated by its ability to sense cytosolic calcium levels via binding to CaM. PMID:27560828

From anatomy to function: diagnosis of atherosclerotic renal artery stenosis.

PubMed

Odudu, Aghogho; Vassallo, Diana; Kalra, Philip A

2015-12-01

Atherosclerotic renal artery stenosis (ARAS) affects 7% of the over 65 s and will be increasingly common with an ageing population. ARAS obstructs normal renal perfusion with adverse renal and cardiovascular consequences. Drug therapy is directed at reducing atherosclerotic risk. Two recent major trials of revascularization for ARAS showed that clinical outcomes were not improved beyond those offered by optimal drug therapy in most patients. This reflects experimental data showing that restoration of blood flow alone may not attenuate a cascade of tissue injury. A shift from anatomic to functional imaging of ARAS coupled to novel therapies might improve clinical outcomes in selected patients. This review outlines the case for separately assessing hemodynamic significance of arterial stenosis and functional reserve of renal parenchymal tissue. The authors consider current and emerging diagnostic techniques for ARAS and their potential to allow individualized and functionally directed treatments.

Oral manifestations in a renal osteodystrophy patient - a case report with review of literature.

PubMed

J, Parthiban; Nisha V, Aarthi; Gs, Asokan; Ca, Prakash; Mm, Varadharaja

2014-08-01

Renal Osteodystrophy (ROD) is a common complication of chronic renal disease (CRD) and is the part of a broad spectrum of disorders of mineral metabolism that occurs in the clinical setting. It occurs early in the course of chronic renal failure and progresses as the kidney function deteriorates. It is an osseous alteration believed to arise from increased parathyroid function associated with inappropriate calcium, phosphorus and vitamin D metabolism. Involvement of the jaws is common and radiographic alterations are often one of the earliest signs of chronic renal failure. Herein, reporting a case of Chronic Renal Failure (Bilateral Grade I Neuropathy) with ROD presenting oral manifestations in an 11-year -old male child.

Reversal deterioration of renal function accompanied with primary hypothyrodism.

PubMed

Dragović, Tamara

2012-02-01

Hypothyroidism is often accompanied with decline of kidney function, or inability to maintain electrolyte balance. These changes are usually overlooked in everyday practice. Early recognition of this association eliminates unnecessary diagnostic procedures that postpone the adequate treatment. Two patients with elevated serum creatinine levels due to primary autoimmune hypothyroidism, with complete recovery of creatinine clearance after thyroid hormone substitution therapy are presented. The first patient was a young male whose laboratory tests suggested acute renal failure, and the delicate clinical presentation of reduced thyroid function. The second patient was an elderly woman with a history of a long-term signs and symptoms attributed to ageing, including the deterioration of renal function, with consequently delayed diagnosis of hypothyroidism. Serum thyrotropin and thyroxin levels measurement should be done in all cases of renal failure with undefined renal desease, even if the typical clinical presentation of hypothyroidism is absent. Thyroid hormone assays sholud also be performed in all patients with chronic kidney disease whose kidney function is rapidly worsening.

Renal function monitoring in patients prescribed dabigatran in the Compass Health Primary Health Organisation: a quality improvement audit.

PubMed

McBain, Lynn; Kyle, Anna

2018-03-09

To assess annual renal function monitoring and clinical indications for use in patients prescribed dabigatran. A quality improvement activity included all patients in the Compass Health Primary Health Organisation (PHO) prescribed dabigatran. Information recorded: demographics; indication for use; daily dose; height; weight; serum creatinine; and estimated glomerular filtration rate (eGFR). The first audit occurred during July 2013 - May 2014, the second during May 2014 - October 2016. Across the PHO, all patients prescribed dabigatran were reviewed: 941 patients and 1,564 respectively. At the time of the second pass audit, renal function monitoring improved from 88% to 90%, and 96% were prescribed dabigatran for an approved indication. Results showed a continuing high level of renal function monitoring across the PHO in 90% of patients prescribed dabigatran. Practitioners were reminded to use creatinine clearance as a marker of renal function. Dabigatran was prescribed for an approved indication in 96% of patients. Our results are in line with recommended best practice and clinical guidelines.

Rickets–vitamin D deficiency and dependency

PubMed Central

Sahay, Manisha; Sahay, Rakesh

2012-01-01

Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal. PMID:22470851

Hydroxy double salts intercalated with Mn(II) complexes as potential contrast agents

NASA Astrophysics Data System (ADS)

Jin, Miao; Li, Wanjing; Spillane, Dominic E. M.; Geraldes, Carlos F. G. C.; Williams, Gareth R.; Bligh, S. W. Annie

2016-03-01

A series of Mn(II) aminophosphonate complexes were successfully synthesized and intercalated into the hydroxy double salt [Zn5(OH)8]Cl2·yH2O. Complex incorporation led to an increase in the interlayer spacing from 7.8 to 10-12 Å. Infrared spectroscopy showed the presence of the characteristic vibration peaks of the Mn(II) complexes in the intercalates' spectra, indicating successful incorporation. The complex-loaded composites had somewhat lower proton relaxivities than the pure complexes. Nevertheless, these intercalates may have use as MRI contrast agents for patients with poor kidney function, where traditional Gd(III)-based contrast agents cause severe renal failure.

Risk factors associated with the deterioration of renal function after kidney transplantation.

PubMed

Serón, Daniel; Fulladosa, Xavier; Moreso, Francesc

2005-12-01

Renal function early after transplantation is associated with a large number of risk factors, including donor age and acute rejection. During the 1990s, donor age increased and the incidence of acute rejection decreased. Renal function between the third and sixth month improved slightly, while renal function deterioration between the third or sixth month and the 12th month improved significantly. This modification coincides with the introduction of mycophenolate mofetil and tacrolimus. The tendency for sustained renal improvement early after transplantation became more evident after the introduction of anti-calcineurin-free regimens. Studies of protocol biopsies have shown that there is an increase of glomerular volume after transplantation and that a larger glomerular volume at 4 months is associated with a better glomerular filtration rate. This adaptation mechanism is impaired in patients with chronic allograft nephropathy or in patients with high cyclosporin levels. Taken together, these data suggest that the steady improvement of renal allograft function may be partly explained by a better glomerular adaptation after transplantation because of the avoidance of the vasoconstrictive effect of anti-calcineurinic agents, and a significant decrease in the prevalence of chronic allograft nephropathy early after transplantation.

Impact of Polymyxin B Associated Acute Kidney Injury in 1-Year Mortality and Renal Function Recovery.

PubMed

Gomes, Eduardo C; Falci, Diego R; Bergo, Pedro; Zavascki, Alexandre P; Rigatto, Maria Helena

2018-03-01

To evaluate the impact of polymyxin B (PMB)- associated Acute Kidney Injury (AKI) in 1-year mortality and renal function recovery. Patients >18 years old who survived the first 30-days after PMB therapy were followed for 1-year. The impact of AKI and Renal Failure (using RIFLE score) in 1-year mortality was analyzed, along with other confounding variables. Variables with a P value ≤0.2 were included in a forward stepwise Cox regression model. In the subgroup of patients who developed AKI, we evaluated renal function recovery. A total of 234 patients were included for analyses. Of these, 108 (46.1%) died, in a median time of 63 (38.3-102.5) days. The use of other nephrotoxic drugs along with PMB (P=0.05), renal failure (P=0.03), dialysis (P<0.01) and re-exposure to PMB (P<0.01), were all significantly related to 1-year mortality, while male gender had a protective effect (P=0.01). Independent factors related to death were age (aHR 1.02, 95%CI 1.00-1.03, P=0.02), re-exposure to PMB (aHR 2.69, 95%CI 1.82-3.95, P<0.01), and male gender (aHR0.6, 95%CI 0.41-0.87, P=0.01), when controlled for renal failure (aHR 1.28, 95%CI 0.78-2.10, P=0.34).Thirty one of 94 (33%) patients who developed AKI had renal function recovery within one-year. Mortality rates were high in the first year after PMB use and only one third of patients who develop AKI return to baseline renal function. Strategies to reduce renal toxicity are urgently needed in these patients. Copyright © 2018. Published by Elsevier B.V.

Hemodynamic and neurochemical determinates of renal function in chronic heart failure.

PubMed

Gilbert, Cameron; Cherney, David Z I; Parker, Andrea B; Mak, Susanna; Floras, John S; Al-Hesayen, Abdul; Parker, John D

2016-01-15

Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications. Copyright © 2016 the American Physiological Society.

Impact of estimated glomerular filtration rate based on plasma cystatin C and serum creatinine levels before allogeneic hematopoietic cell transplantation.

PubMed

Wada, Hidenori; Kanda, Junya; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Nakasone, Hideki; Yamazaki, Rie; Kako, Shinichi; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

2018-06-01

No standard method for measuring renal function has been established in allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed 80 patients with hematological diseases who underwent allo-HCT at our center. We assessed renal function using creatinine clearance (Ccr), estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcre), eGFR based on cystatin C (eGFRcys), and the average of eGFRcre and eGFRcys (eGFRave). We then evaluated the impact of pre-transplant renal function on the exacerbation of renal function and non-relapse mortality after transplantation. There was a significant correlation between Ccr and eGFRcre, eGFRcys, and eGFRave. eGFRave best predicted the exacerbation of renal function according to the area under the receiver-operating characteristic curve. The cumulative incidence of renal function exacerbation at 1 year was higher in the lower eGFRave group (<90 ml/min/1.73 m 2 ) than in the higher eGFRave group (≥90 ml/min/1.73 m 2 ; 0.85 vs. 0.39, p < 0.001), which was confirmed by a multivariate analysis (HR 2.75, p = 0.001). A lower eGFRave value was a marginally significant factor for non-relapse mortality (HR 3.29, p = 0.076). Among the four parameters, eGFRave best predicted the exacerbation of renal function in allo-HCT. Further, the marginal association between low eGFRave and high non-relapse mortality warrants further study in a prospective study in allo-HCT.

Pharmacokinetic Properties of Fostamatinib in Patients With Renal or Hepatic Impairment: Results From 2 Phase I Clinical Studies.

PubMed

Martin, Paul; Oliver, Stuart; Gillen, Michael; Marbury, Thomas; Millson, David

2015-12-01

Phase III trials of fostamatinib, an oral spleen tyrosine kinase inhibitor, in the treatment of rheumatoid arthritis have been completed. Herein, we report the effects of renal and hepatic impairment on the pharmacokinetic (PK) properties of the active metabolite of fostamatinib, R406, in plasma, and on the urinary excretion of R406 and its metabolite N-glucuronide. Two Phase I, single-center, open-label clinical trials determined the PK properties and tolerability of fostamatinib in subjects with normal or impaired renal or hepatic function. Twenty-four subjects in the study in renal impairment (8 per group: normal renal function, moderate renal dysfunction, or end-stage renal disease [ESRD]), and 32 subjects in the study in hepatic impairment (8 per group: normal hepatic function or mild, moderate, or severe hepatic impairment) received a single 150-mg dose of fostamatinib. Patients with ESRD in the study in renal impairment participated in 2 treatment periods separated by a ≥1-week washout. In these patients, fostamatinib was administered after dialysis or 2 hours before dialysis. Geometric mean R406 Cmax and AUC values were less in the combined renally impaired group than in the group with normal renal function; Tmax was similar across groups. However, renal impairment had no apparent effect considered clinically relevant on unbound R406. In patients with ESRD, R406 exposure was less when fostamatinib was administered after compared with before dialysis. Urinary excretion of R406 N-glucuronide was decreased with increasing severity of renal impairment. Renal elimination of R406 was negligible in all groups. Varying degrees of hepatic impairment had no consistent effects on the PK properties of R406. R406 Cmax values were 10% to 15% less in all hepatically impaired groups than in the group with normal hepatic function. AUC and Tmax values were similar between the groups with normal and severely impaired hepatic function; in the groups with mild or moderate hepatic impairment, AUC was less and Tmax was greater. The geometric mean percentage of unbound R406 ranged from 0.64% to 1.95% and was greatest in the group with severe hepatic impairment. The urinary excretion of R406 was minimal. The amount of R406 N-glucuronide excreted in urine was greater in severely hepatically impaired patients. Fostamatinib 150 mg was generally well tolerated. In these patients, renal or hepatic impairment did not affect exposure to the active metabolite of fostamatinib, R406, to a clinically relevant extent. ClinicalTrials.gov identifiers: NCT01245790 (renal) and NCT01222455 (hepatic). Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Impact of Stone Removal on Renal Function: A Review

PubMed Central

Wood, Kyle; Keys, Tristan; Mufarrij, Patrick; Assimos, Dean G

2011-01-01

Stone removal can improve renal function by eradicating obstruction and, in certain cases, an underlying infection. Stone-removing procedures, however, may negatively impact functional integrity. Many things may impact the latter, including the procedures used, the methods of assessing function, the time when these assessments are made, the occurrence of complications, the baseline condition of the kidney, and patient-related factors. In the majority of cases, little significant functional impairment occurs. However, there are gaps in our knowledge of this subject, including the cumulative effects of multiple procedures violating the renal parenchyma and long-term functional outcomes. PMID:21935339

Biomarkers for acute kidney injury in decompensated cirrhosis: A Prospective Study.

PubMed

Jaques, David A; Spahr, Laurent; Berra, Gregory; Poffet, Vincent; Lescuyer, Pierre; Gerstel, Eric; Garin, Nicolas; Martin, Pierre-Yves; Ponte, Belen

2018-01-25

Acute kidney injury (AKI) is a frequent complication in cirrhotic patients. As serum creatinine is a poor marker of renal function in this population, we aimed to study the utility of several biomarkers in this context. A prospective study was conducted in hospitalized patients with decompensated cirrhosis. Serum creatinine (SCr), Cystatin C (CystC), NGAL and urinary NGAL, KIM-1, protein, albumin and sodium were measured on three separate occasions. Renal resistive index (RRI) was obtained. We analyzed the value of these biomarkers to determine the presence of AKI, its etiology [prerenal, acute tubular necrosis (ATN), or hepatorenal (HRS)], its severity and a composite clinical outcome at 30 days (death, dialysis and intensive care admission). We included 105 patients, of which 55 had AKI. SCr, CystC, NGAL (plasma and urinary), urinary sodium and RRI at inclusion were independently associated with the presence of AKI. SCr, CystC and plasma NGAL were able to predict the subsequent development of AKI. Pre-renal state showed lower levels of SCr, NGAL (plasma and urinary) and RRI. ATN patients had high levels of NGAL (plasma and urinary) as well as urinary protein and sodium. HRS patients presented an intermediate pattern. All biomarkers paralleled the severity of AKI. SCr, CystC and plasma NGAL predicted the development of the composite clinical outcome with the same performance as the MELD score. In patients with decompensated cirrhosis, early measurement of renal biomarkers provides valuable information on AKI etiology. It could also improve AKI diagnosis and prognosis. This article is protected by copyright. All rights reserved.

Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals With Renal Impairment.

PubMed

Heinig, Roland; Kimmeskamp-Kirschbaum, Nina; Halabi, Atef; Lentini, Silvia

2016-11-01

Finerenone (BAY 94-8862) is a nonsteroidal mineralocorticoid receptor antagonist in development for the treatment of diabetic kidney disease. This observational trial compared the pharmacokinetics of a single oral dose of finerenone 10 mg (immediate-release tablet) in adults with mild (creatinine clearance [CL CR ] 50-80 mL/min; n = 8), moderate (CL CR 30 to < 50 mL/min; n = 8), or severe (CL CR < 30 mL/min; n  =  9) renal impairment with those in adults with normal renal function (CL CR > 80 mL/min; n  = 8) over 96 hours postdose. Exposure to finerenone was not affected by mild renal impairment. In participants with moderate or severe renal impairment, exposure to finerenone was increased compared with those with normal renal function (increase in area under the curve for unbound finerenone, 57.1% [outlier excluded] and 46.5%, respectively), with moderate to high interindividual variability. Renal impairment had no consistent effect on the maximum plasma concentration, C max (differences in C max for unbound finerenone of +12% and -7% with moderate [outlier excluded] and severe impairment vs normal renal function, respectively). Renal elimination of finerenone is minimal. However, changes in exposure may occur because of the effects of renal impairment on nonrenal routes of elimination. © 2016, The American College of Clinical Pharmacology.

Renal artery stent fracture with refractory hypertension: a case report and review of the literature.

PubMed

Chua, Su-Kiat; Hung, Huei-Fong

2009-07-01

A 73-year-old man with resistant hypertension and impaired renal function underwent stenting for right renal artery (RRA) stenosis. Two years later, he presented with uncontrolled hypertension and worse renal function. Renal arteriogram revealed RRA stent fracture with in-stent restenosis. Another stent was deployed. Four months later, however, renal arteriogram revealed in-stent restenosis again. This time, balloon angioplasty alone was performed. He had been symptom-free with stable condition at 2-year follow-up. A literature review disclosed six renal artery stent fracture cases, including the present one, who developed in-stent stenosis resulted from stent fracture. Two major anatomy features of renal artery stenosis were suggestive for development of stent fracture: (1) renal artery entrapment by diaphragmatic crus, and (2) mobile kidney with acute angulation at proximal segment of the renal artery. It is important to detect this etiology of renal artery stenosis because stenting in these vessels may contribute to in-stent restenosis or stent fracture. Management of renal artery stent fracture, including endovascular treatment or aortorenal bypass, should be considered on a case-by-case basis in relation to clinical settings. Copyright 2009 Wiley-Liss, Inc.

MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

PubMed

Wentland, Andrew L; Artz, Nathan S; Fain, Sean B; Grist, Thomas M; Djamali, Arjang; Sadowski, Elizabeth A

2012-01-01

Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P < 1 × 10(-6)) and oxygen bioavailability (Spearman's correlation coefficient = -0.60; P < 0.0001) correlated significantly with TRBF, whereas medullary perfusion and oxygen bioavailability did not correlate with TRBF. Our results demonstrate expected changes given the pharmacologically induced changes in renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all three parameters of kidney function in a single MRI examination and to evaluate the relationships between these functional parameters is potentially useful for evaluating the state of the human kidneys in situ in future studies.

Parathyroidectomy Halts the Deterioration of Renal Function in Primary Hyperparathyroidism.

PubMed

Tassone, Francesco; Guarnieri, Andrea; Castellano, Elena; Baffoni, Claudia; Attanasio, Roberto; Borretta, Giorgio

2015-08-01

Decreased renal function has been consistently included among factors prompting recommendation for surgery in primary hyperparathyroidism (PHPT). However, most retrospective studies addressing this issue did not show an improvement in renal function after parathyroidectomy (PTX). The aim of this study was to investigate changes in renal function after PTX in PHPT patients subdivided according to renal function at diagnosis. This was a retrospective cross-sectional study. We studied 109 consecutive PHPT patients before and after PTX. Biochemical evaluation included fasting total and ionized serum calcium, phosphate, creatinine, immunoreactive intact PTH, and 25-hydroxyvitamin D3 levels. Glomerular filtration rate (GFR) was assessed with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Mean (± SD) CKD-EPI estimated GFR (eGFR) at diagnosis was 82.4 ± 19.3 mL/min/1.73 m(2) (median, 84.8 mL/min/1.73 m(2); interquartile range, 68.5-94.2 mL/min/1.73 m(2)). Patients with eGFR equal to or higher than 60 mL/min/1.73 m(2) (group 1, n = 95) were significantly younger than patients with eGFR lower than 60 mL/min/1.73 m(2) (group 2, n = 14; P < .0003). After PTX, eGFR did not change in patients of group 2 (P = .509), whereas it was significantly reduced in patients of group 1 (P < .0002). The difference in eGFR between baseline and post-PTX values was correlated negatively with baseline serum creatinine (R = -0.27; P = .0052) and positively with baseline CKD-EPI eGFR (R = 0.32; P = .00062). At multiple regression analysis, only systolic blood pressure and baseline CKD-EPI eGFR were independent predictors of GFR variation. Surgical cure of PHPT halts renal function deterioration in patients with coexisting renal disease. Our study thus supports the indication for surgery in patients with eGFR less than 60 mL/min/1.73 m(2), as recommended by current guidelines. Moreover, our data show that presurgical renal function is a relevant predictor of renal function after PTX.

Treatment options for renal cell carcinoma in renal allografts: a case series from a single institution.

PubMed

Swords, Darden C; Al-Geizawi, Samer M; Farney, Alan C; Rogers, Jeffrey; Burkart, John M; Assimos, Dean G; Stratta, Robert J

2013-01-01

Renal cell carcinoma (RCC) is more common in renal transplant and dialysis patients than the general population. However, RCC in transplanted kidneys is rare, and treatment has previously consisted of nephrectomy with a return to dialysis. There has been recent interest in nephron-sparing procedures as a treatment option for RCC in allograft kidneys in an effort to retain allograft function. Four patients with RCC in allograft kidneys were treated with nephrectomy, partial nephrectomy, or radiofrequency ablation. All of the patients are without evidence of recurrence of RCC after treatment. We found nephron-sparing procedures to be reasonable initial options in managing incidental RCCs diagnosed in functioning allografts to maintain an improved quality of life and avoid immediate dialysis compared with radical nephrectomy of a functioning allograft. However, in non-functioning renal allografts, radical nephrectomy may allow for a higher chance of cure without the loss of transplant function. Consequently, radical nephrectomy should be utilized whenever the allograft is non-functioning and the patient's surgical risk is not prohibitive. © 2013 John Wiley & Sons A/S.

Implementation of Get with the Guideline Acute Myocardial Infarction Program at Johns Hopkins Hospital and Its Effect on Core Measures

DTIC Science & Technology

2007-05-25

allergy E Patient is discharged on hydralazine/nitrate therapy* E Hypotension* El Moderate or severe aortic stenosis El Worsening renal function* E...Hypotension* E Moderate or severe aortic stenosis El Worsening renal function* E Hyperkalemia* E Bilateral renal artery stenosis * E Pregnancy* E Other...Hyperkalemia* El Bilateral renal artery stenosis * E Pregnancy* El Other - must be documented in medical record Angiotension Receptor Blocker (ARB

[Hereditary cerebro-oculo-renal syndromes].

PubMed

Sessa, Galina; Hjortshøj, Tina Duelund; Egfjord, Martin

2014-02-17

Although many congenital diseases present disturbances of the central nervous system, eyes and renal function, only few of these have a defined genetic basis. The first clinical features of cerebro-oculo-renal diseases usually develop in early childhood and deterioration of kidney function and even end-stage kidney disease may occur in a young age. The syndromes should be considered in patients with retarded growth and development, central nervous system abnormalities, impaired vision or blindness and progressive renal failure.

[A case report of simultaneous liver, pancreas-duodenum, and kidney transplantation in a patient with post-hepatitic cirrhosis combined with uremia and insulin-dependent diabetes related to chronic pancreatitis].

PubMed

Wang, He; Dou, Ke-feng; Yang, Xiao-jian; Qin, Wei-jun; Zhang, Geng; Yu, Lei; Kang, Fu-xia; Chen, Shao-yang; Xiong, Li-ze; Song, Zhen-shun; Liu, Zheng-cai

2006-09-12

To study the effect of triple organ transplantation (liver, kidney, and pancreas) in patient of end-stage liver disease with renal failure and diabetes, and to explore the optimal surgical procedure. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation was performed on a 43-year-old male patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to chronic pancreatitis (CP) who developed hepatic and renal failure. The pancreatic exocrine secretions were drained enterically to the jejunum. Prednisone, tacrolimus, mycophenolate mofetil, and ATG were used as immunosuppression therapy. Good liver and pancreas allograft function recovery was achieved within 7 days after the operation. And the recovery of renal allograft function was delayed. The renal allograft was removed because of break-down of renal blood flow 16 days after the transplantation. A new renal transplantation was performed at the same position. The second kidney graft recovered its normal function 3 days later. Up to the writing of this paper no acute rejection of organs and such complications as pancreatitis, thrombosis, and localized infection occurred. The patient became insulin independent with normal liver and renal function. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation can be a good method for the patients with exocrine pancreatic insufficiency and insulin-dependent diabetes combined with hepatic and renal failure.

Treatment of Acute Renal Failure Secondary to Multiple Myeloma with Chemotherapy and Extended High Cut-Off Hemodialysis

PubMed Central

Hutchison, Colin A.; Bradwell, Arthur R.; Cook, Mark; Basnayake, Kolitha; Basu, Supratik; Harding, Stephen; Hattersley, John; Evans, Neil D.; Chappel, Mike J.; Sampson, Paul; Foggensteiner, Lukas; Adu, Dwomoa; Cockwell, Paul

2009-01-01

Background and objectives: Extended hemodialysis using a high cut-off dialyzer (HCO-HD) removes large quantities of free light chains in patients with multiple myeloma. However, the clinical utility of this method is uncertain. This study assessed the combination of chemotherapy and HCO-HD on serum free light chain concentrations and renal recovery in patients with myeloma kidney (cast nephropathy) and dialysis-dependent acute renal failure. Design, setting, participants, & measurements: An open-label study of the relationship between free light chain levels and clinical outcomes in 19 patients treated with standard chemotherapy regimens and HCO-HD. Results: There were sustained early reductions in serum free light chain concentrations (median 85% [range 50 to 97]) in 13 patients. These 13 patients became dialysis independent at a median of 27 d (range 13 to 120). Six patients had chemotherapy interrupted because of early infections and did not achieve sustained early free light chain reductions; one of these patients recovered renal function (at 105 d) the remaining 5 patients did not recover renal function. Patients who recovered renal function had a significantly improved survival (P < 0.012). Conclusion: In dialysis-dependent acute renal failure secondary to myeloma kidney, patients who received uninterrupted chemotherapy and extended HCO-HD had sustained reductions in serum free light chain concentrations and recovered independent renal function. PMID:19339414

Clinical Correlates and Prognostic Value of Proenkephalin in Acute and Chronic Heart Failure.

PubMed

Matsue, Yuya; Ter Maaten, Jozine M; Struck, Joachim; Metra, Marco; O'Connor, Christopher M; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G; Givertz, Michael M; Bloomfield, Daniel M; Dittrich, Howard C; van Veldhuisen, Dirk J; van der Meer, Peter; Damman, Kevin; Voors, Adriaan A

2017-03-01

Proenkephalin (pro-ENK) has emerged as a novel biomarker associated with both renal function and cardiac function. However, its clinical and prognostic value have not been well evaluated in symptomatic patients with heart failure. The association between pro-ENK and markers of renal function was evaluated in 95 patients with chronic heart failure who underwent renal hemodynamic measurements, including renal blood flow (RBF) and glomerular filtration rate (GFR) with the use of 131 I-Hippuran and 125 I-iothalamate clearances, respectively. The association between pro-ENK and clinical outcome in acute heart failure was assessed in another 1589 patients. Pro-ENK was strongly correlated with both RBF (P < .001) and GFR (P < .001), but not with renal tubular markers. In the acute heart failure cohort, pro-ENK was a predictor of death through 180 days, heart failure rehospitalization through 60 days, and death or cardiovascular or renal rehospitalization through day 60 in univariable analyses, but its predictive value was lost in a multivariable model when other renal markers were entered in the model. In patients with chronic and acute heart failure, pro-ENK is strongly associated with glomerular function, but not with tubular damage. Pro-ENK provides limited prognostic information in patients with acute heart failure on top of established renal markers. Copyright © 2016 Elsevier Inc. All rights reserved.

The canonical wnt signal restricts the glycogen synthase kinase 3/fbw7-dependent ubiquitination and degradation of eya1 phosphatase.

PubMed

Sun, Ye; Li, Xue

2014-07-01

Haploinsufficiency of Eya1 causes the branchio-oto-renal (BOR) syndrome, and abnormally high levels of Eya1 are linked to breast cancer progression and poor prognosis. Therefore, regulation of Eya1 activity is key to its tissue-specific functions and oncogenic activities. Here, we show that Eya1 is posttranslationally modified by ubiquitin and that its ubiquitination level is self-limited to prevent premature degradation. Eya1 has an evolutionarily conserved CDC4 phosphodegron (CPD) signal, a target site of glycogen synthase kinase 3 (GSK3) kinase and Fbw7 ubiquitin ligase, which is required for Eya1 ubiquitination. Genetic deletion of Fbw7 and pharmacological inhibition of GSK3 significantly decrease Eya1 ubiquitination. Conversely, activation of the phosphatidylinositol 3-kinase (PI3K)/Akt and the canonical Wnt signal suppresses Eya1 ubiquitination. Compound Eya1(+/-); Wnt9b(+/-) mutants exhibit an increased penetrance of renal defect, indicating that they function in the same genetic pathway in vivo. Together, these findings reveal that the canonical Wnt and PI3K/Akt signal pathways restrain the GSK3/Fbw7-dependent Eya1 ubiquitination, and they further suggest that dysregulation of this novel axis contributes to tumorigenesis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Single-dose rATG induction at renal transplantation: superior renal function and glucoregulation with less hypomagnesemia.

PubMed

Stevens, R Brian; Lane, James T; Boerner, Brian P; Miles, Clifford D; Rigley, Theodore H; Sandoz, John P; Nielsen, Kathleen J; Skorupa, Jill Y; Skorupa, Anna J; Kaplan, Bruce; Wrenshall, Lucile E

2012-01-01

Rabbit anti-thymocyte globulin (rATG) induction reduces reperfusion injury and improves renal function in kidney recipients by means of properties unrelated to T-cell lysis. Here, we analyze intensive rATG induction (single dose, rATG(S) , vs. divided dose, rATG(D) ) for improved renal function and protection against hyperglycemia. Patients without diabetes (n = 98 of 180) in a prospective randomized trial of intensive rATG induction were followed for six months for the major secondary composite end point of impaired glucose regulation (hyperglycemia and new-onset diabetes after transplantation, NODAT). Prospectively collected data included fasting blood glucose and HbA(1c). Serum Mg(++) was routinely collected and retrospectively analyzed. Induction with rATG(S) produced less impaired glucose regulation (p = 0.05), delayed NODAT development (p = 0.02), less hyperglycemia (p = 0.02), better renal function (p = 0.04), and less hypomagnesemia (p = 0.02), a factor associated with a lower incidence of NODAT. Generalized linear modeling confirmed that rATG(S) protects against a synergistic interaction between tacrolimus and sirolimus that otherwise increased hypomagnesemia (p = 0.008) and hyperglycemia (p = 0.03). rATG(S) initiated before renal reperfusion improved early renal function and reduced impaired glucose regulation, an injury by diabetogenic maintenance agents (tacrolimus and sirolimus). © 2011 John Wiley & Sons A/S.

Renal function and plasma volume following ultramarathon cycling.

PubMed

Neumayr, G; Pfister, R; Hoertnagl, H; Mitterbauer, G; Prokop, W; Joannidis, M

2005-01-01

In recreational cyclists marathon cycling influences renal function only on a minimal scale. Respective information on extreme ultramarathon cycling in better trained athletes is not available. The objective was to evaluate the renal and haematological effects of ultraendurance cycling in the world's best ultramarathon cyclists. Creatinine (CR), urea, haemoglobin (Hb), haematocrit (Hct) and plasma volume (PV) were investigated in 16 male ultramarathon cyclists during the 1st Race Across the Alps in 2001 (distance: 525 km; cumulative altitude difference: 12,600 m). All renal functional parameters were normal pre-exercise. During the race serum CR, urea and uric acid rose significantly by 33, 97 % and 18 % (p <0.001 respectively) and nearly normalised again on the following day. The decline in calculated CR clearance was 25 %. There was a negative correlation (r=- 0.575, p=0.02) between the rise in serum CR and the athlete's training kilometers. The serum urea/CR ratio rose above 40 in 12 athletes (75 %). Mean fractional sodium excretion and fractional uric acid excretion fell below 0.5 % (p <0.001) and 7 %, indicating reduced renal perfusion. The deflection of the renal functional parameters was temporary and nearly gone after 24 hours of recovery. Hct declined during the race from 0.44 to 0.42, and continued falling on the next day (0.42 --> 0.40; p <0.001). The corresponding rises in calculated PV were + 8 % and + 22 %. The study affirms that in world class cyclists the enormous strains of ultramarathon cycling influence renal function only on a minimal scale. The impact on the PV, however, is pronounced leading to marked haemodilution post-exercise. This very temporary "impairment of renal function" seems to be the physiological response to ultramarathon cycling and may be attenuated to some extent by preceding high-volume training.

Pharmacokinetics and Tolerability of Lorcaserin in Special Populations: Elderly Patients and Patients with Renal or Hepatic Impairment.

PubMed

Christopher, Ronald J; Morgan, Michael E; Tang, Yong; Anderson, Christen; Sanchez, Matilde; Shanahan, William

2017-04-01

To determine whether dosage adjustment is likely to be necessary for effective and well-tolerated use of a pharmaceutical agent, guidance documents from the US Food and Drug Administration recommend pharmacokinetics studies in patients with impaired renal or impaired hepatic function and in the elderly population. Three studies were conducted to evaluate the pharmacokinetic properties and tolerability of lorcaserin in these populations. Lorcaserin was evaluated in single-dose pharmacokinetics studies of 3 overweight/obese populations: (1) elderly (aged >65 years) patients; (2) patients with impaired renal function; and (3) those with impaired hepatic function. In elderly patients, C max was lower (geometric mean ratio [GMR], 0.83; 90% CI, 0.71-0.97), but AUC was unchanged versus adult patients. In patients with renal impairment, C max was reduced versus that in patients with normal renal function (GMR: mild impairment, 0.99 [90% CI, 0.76-1.29]; moderate, 0.70 [90% CI, 0.54-0.90]; and severe, 0.69 [90% CI, 0.53-0.89]); no trend in AUC was observed in this group versus renal impairment. In patients with hepatic impairment, C max was decreased (GMR: mild impairment, 0.92 [90% CI, 0.76-1.11]; moderate, 0.86 [90% CI, 0.71-1.04]), and AUC was increased versus patients with normal hepatic function. Based on these findings, no lorcaserin dose adjustments are necessary in elderly patients with normal renal function or in patients with mild/moderate renal or hepatic impairment. ClinicalTrials.gov identifiers: NCT00828581, NCT00828438, and NCT00828932. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Renal uptake and tolerability of a 2'-O-methoxyethyl modified antisense oligonucleotide (ISIS 113715) in monkey.

PubMed

Henry, Scott P; Johnson, Mark; Zanardi, Thomas A; Fey, Robert; Auyeung, Diana; Lappin, Patrick B; Levin, Arthur A

2012-11-15

The primary target organ for uptake of systemically administered phosphorothioate oligonucleotides is the kidney cortex and the proximal tubular epithelium in particular. To determine the effect of oligonucleotide uptake on renal function, a detailed renal physiology study was performed in cynomolgus monkeys treated with 10-40 mg/kg/week ISIS 113715 for 4 weeks. The concentrations of oligonucleotide in the kidney cortex ranged from 1400 to 2600 μg/g. These concentrations were associated with histologic changes in proximal tubular epithelial cells that ranged from the appearance of cytoplasmic basophilic granules to atrophic and degenerative changes at higher concentrations. However, there were no renal functional abnormalities as determined by the typical measurements of blood urea nitrogen, serum creatinine, creatinine clearance, or urine specific gravity. Nor were there changes in glomerular filtration rate, or renal blood flow. Specific urinary markers of tubular epithelial cell damage, such as N-acetyl-glucosaminidase, and α-glutathione-s-transferase were not affected. Tubular function was further evaluated by monitoring the urinary excretion of amino acids, β(2)-microglobulin, or glucose. Renal function was challenged by administering a glucose load and by examining concentrating ability after a 4-h water deprivation. Neither challenge produced any evidence of change in renal function. The only change observed was a low incidence of increased urine protein/creatinine ratio in monkeys treated with ≥40 mg/kg/week which was rapidly reversible. Collectively, these data indicate that ISIS 113715-uptake by the proximal tubular epithelium has little or no effect on renal function at concentrations of 2600 μg/g. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Renal Function, Bisphenol A, and Alkylphenols: Results from the National Health and Nutrition Examination Survey (NHANES 2003–2006)

PubMed Central

You, Li; Zhu, Xiangzhu; Shrubsole, Martha J.; Fan, Hong; Chen, Jing; Dong, Jie; Hao, Chuan-Ming; Dai, Qi

2011-01-01

Background Urinary excretion of bisphenol A (BPA) and alkylphenols (APs) was used as a biomarker in most previous studies, but no study has investigated whether urinary excretion of these environmental phenols differed by renal function. Objective We estimated the association between renal function and urinary excretion of BPA and APs. Methods Analyses were conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2003–2006. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) Study equation and by the newly developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Regression models were used to calculate geometric means of urinary BPA and APs excretion by eGFR category (≥ 90, 60–90, < 60 mL/min/m2) after adjusting for potential confounding factors. Results When we used the MDRD Study equation, participants without known renal disease (n = 2,573), 58.2% (n = 1,499) had mildly decreased renal function or undiagnosed chronic kidney disease. The adjusted geometric means for urinary BPA excretion decreased with decreasing levels of eGFR (p for trend = 0.04). The associations appeared primarily in females (p for trend = 0.03). Urinary triclosan excretion decreased with decreasing levels of eGFR (p for trend < 0.01) for both males and females, and the association primarily appeared in participants < 65 years of age. The association between BPA and eGFR was nonsignificant when we used the CKD-EPI equation. Conclusions Urinary excretion of triclosan, and possibly BPA, decreased with decreasing renal function. The associations might differ by age or sex. Further studies are necessary to replicate our results and understand the mechanism. PMID:21147601

Hydrocarbon exposure may cause glomerulonephritis and worsen renal function: evidence based on Hill's criteria for causality.

PubMed

Ravnskov, U

2000-08-01

Many observational and experimental studies point to hydrocarbon exposure as an important pathogenic factor in glomerulonephritis. The findings have made little impact on current concepts and patient care, possibly because the hypothesis of a direct causal effect of the exposure and the hypothesis that the exposure worsens renal function have not been considered separately. This review examines these two hypotheses using Hill's criteria for causality. The results from 14 cross-sectional, 18 case-control studies, two cohort studies, 15 experiments on laboratory animals and two on human beings together with many case reports satisfy all but one of Hill's criteria for both hypotheses. Of particular importance is the finding in the case-control and follow-up studies of an association between degree of exposure and stage of renal disease, and an inverse association between degree of exposure and renal function, indicating that the most important effect of hydrocarbon exposure is its effect on renal function. End-stage renal failure may be preventable in many patients with glomerulonephritis provided a possible exposure to toxic chemicals is discontinued.

[Acetaminophen (paracetamol) causing renal failure: report on 3 pediatric cases].

PubMed

Le Vaillant, J; Pellerin, L; Brouard, J; Eckart, P

2013-06-01

Renal failure secondary to acetaminophen poisoning is rare and occurs in approximately 1-2 % of patients with acetaminophen overdose. The pathophysiology is still being debated, and renal acetaminophen toxicity consists of acute tubular necrosis, without complication if treated promptly. Renal involvement can sometimes occur without prior liver disease, and early renal manifestations usually occur between the 2nd and 7th day after the acute acetaminophen poisoning. While therapy is exclusively symptomatic, sometimes serious metabolic complications can be observed. The monitoring of renal function should therefore be considered as an integral part of the management of children with acute, severe acetaminophen intoxication. We report 3 cases of adolescents who presented with acute renal failure as a result of voluntary drug intoxication with acetaminophen. One of these 3 girls developed severe renal injury without elevated hepatic transaminases. None of the 3 girls' renal function required hemodialysis, but one of the 3 patients had metabolic complications after her acetaminophen poisoning. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Renal neural mechanisms in salt-sensitive hypertension.

PubMed

DiBona, G F

1995-01-01

Genetic forms of salt (NaCl)-sensitive hypertension are characterized by increased renal sympathetic nerve activity responses to environmental stimuli. The increases in renal sympathetic nerve activity produce marked changes in renal function with renal vasoconstriction and sodium and water retention which can contribute to the initiation, development and maintenance of hypertension. In genetic forms of NaCl-sensitive hypertension, increased dietary NaCl intake produces alterations in norepinephrine kinetics with decreased concentrations of norepinephrine in regions of the anterior hypothalamus which are critical for the regulation of peripheral sympathetic nerve activity. This local central decrease in tonic alpha 2 adrenoceptor sympathoinhibitory input leads to increased peripheral (renal) sympathetic nerve activity and hypertension. Similarly, with increased dietary NaCl intake, patients with NaCl-sensitive hypertension develop increased arterial pressure, renal vasoconstriction, increased glomerular capillary pressure and increased urinary albumin excretion. Thus, increased dietary NaCl intake can, via central nervous system actions, produce increases in renal sympathetic nerve activity whose renal functional effects contribute to the pathophysiology of hypertension.

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

Treatment of multiple synchronous misdiagnosed renal cell cancers in a young patient affected by a "de novo" Von Hippel-Lindau syndrome.

PubMed

Allasia, Marco; Battaglia, Antonino; Pasini, Barbara; Gazzera, Carlo; Calandri, Marco; Bosio, Andrea; Gontero, Paolo; Destefanis, Paolo

2017-02-28

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited syndrome occurring in one out of 36,000 live births. Diagnosis could be a challenge in patients with no familial VHL history. Renal cancer (RCC) represents one of the most important manifestations. RCC is usually recurrent and multifocal. Actually treating RCC in VHL patients represent a clinical dilemma: the oncological outcomes must be balanced against renal function preservation. A young man with a negative familial history was referred to our department with seven misdiagnosed renal masses. VHL disease was determined through genetic test. The multiple RCCs were treated by surgery and percutaneous thermal ablation by radiofrequency ablation (RFA) with complete control of RCC and no impairment of renal function. This case history confirms that VHL disease has to be suspected in young patients with evidence of synchronous multiple renal masses and in presence of specific clinical criteria.RFA appears to be safe in terms of oncological radicalism and in renal function preservation.In hereditary RCC, we should purpose, whenever it is possible, minimally invasive treatment in terms of low hospital stay and a minimal loss of renal tissue.

Germanium in ginseng is low and causes no sodium and water retention or renal toxicity in the diuretic-resistant rats

PubMed Central

Tan, Chunjiang; Xiao, Lu; Chen, Wenlie

2015-01-01

Ginseng preparations contain high concentrations of germanium (Ge), which was reported to contribute to diuretic resistance or renal failure. However, Ge content in ginseng and the influence on renal functions remain unclear. Forty rats were randomly divided into control group, low, moderate, and high Ge ginseng-treated group and observed for 25 days. Daily urine, renal functions, and serum and urine electrolytics were measured. Ge retention in the organs and renal histological changes were also evaluated. Ge content ranged from 0.007 to 0.450 µg/g in various ginseng samples. Four groups showed no difference in the daily urine output, glomerular filtration rate, urinary electrolytes excretions, 24 h-urine protein, as well as plasma and urine urea nitrogen, creatinine, osmotic pressure, and pH values. Ge did not cause any renal pathological effects in this study. No Na and water retention was detected in the ginseng-treated groups. Ge retention in various organs was found highest in spleen, followed by the kidney, liver, lung, stomach, heart, and pancreas. The total Ge contents in various ginsengs were low, and ginseng treatment did not affect renal functions or cause renal histological changes. PMID:25711879

Use of Oral Bisphosphonates by Older Adults with Fractures and Impaired Renal Function

PubMed Central

Sadowski, Cheryl A; Spencer, Tara; Yuksel, Nese

2011-01-01

Background: The manufacturers of oral bisphosphonates (alendronate, risedronate) recommend avoiding use of these drugs in patients with renal impairment. However, many patients who have osteoporosis or who are at risk of fracture are elderly and may have renal impairment. This situation poses a quandary for clinicians in deciding how best to manage osteoporosis in this high-risk population. Objective: To synthesize published evidence regarding the use and safety of oral bisphosphonates for patients with impaired renal function. Methods: The following databases were searched up to October 2010: PubMed, MEDLINE, Embase, the Cochrane Library, and International Pharmaceutical Abstracts. The following key words and terms were used for the searches: bisphosphonates, alendronate, risedronate, Fosamax, Actonel, “renal failure”, “renal insufficiency”, “chronic kidney disease”, and “end-stage renal disease”. The manufacturers of Fosamax and Actonel were asked to provide information about use of their products in patients with renal impairment, including unpublished pharmacokinetic studies or reports of adverse drug events. Results: The search yielded 2 post hoc analyses of safety data, 1 case–control study, 1 case series, 4 retrospective chart analyses, and 2 prospective studies. According to these publications, numerous patients with decreased renal function have received bisphosphonates and have experienced improvement in bone mineral density and/or reduction in risk of fractures, with no increase in adverse effects. Increased renal damage occurred in some individuals with underlying renal disorders, as described in case reports. Conclusions: Although the literature is limited, there is evidence that alendronate and risedronate are well tolerated and effective when used by individuals with renal impairment. Further research is required to confirm the benefits and risks of using these medications in patients with renal impairment. PMID:22479027

Diagnostic accuracy of calculated serum osmolarity to predict dehydration in older people: adding value to pathology laboratory reports.

PubMed

Hooper, Lee; Abdelhamid, Asmaa; Ali, Adam; Bunn, Diane K; Jennings, Amy; John, W Garry; Kerry, Susan; Lindner, Gregor; Pfortmueller, Carmen A; Sjöstrand, Fredrik; Walsh, Neil P; Fairweather-Tait, Susan J; Potter, John F; Hunter, Paul R; Shepstone, Lee

2015-10-21

To assess which osmolarity equation best predicts directly measured serum/plasma osmolality and whether its use could add value to routine blood test results through screening for dehydration in older people. Diagnostic accuracy study. Older people (≥65 years) in 5 cohorts: Dietary Strategies for Healthy Ageing in Europe (NU-AGE, living in the community), Dehydration Recognition In our Elders (DRIE, living in residential care), Fortes (admitted to acute medical care), Sjöstrand (emergency room) or Pfortmueller cohorts (hospitalised with liver cirrhosis). Directly measured serum/plasma osmolality: current dehydration (serum osmolality>300 mOsm/kg), impending/current dehydration (≥295 mOsm/kg). 39 osmolarity equations calculated using serum indices from the same blood draw as directly measured osmolality. Across 5 cohorts 595 older people were included, of whom 19% were dehydrated (directly measured osmolality>300 mOsm/kg). Of 39 osmolarity equations, 5 showed reasonable agreement with directly measured osmolality and 3 had good predictive accuracy in subgroups with diabetes and poor renal function. Two equations were characterised by narrower limits of agreement, low levels of differential bias and good diagnostic accuracy in receiver operating characteristic plots (areas under the curve>0.8). The best equation was osmolarity=1.86×(Na++K+)+1.15×glucose+urea+14 (all measured in mmol/L). It appeared useful in people aged ≥65 years with and without diabetes, poor renal function, dehydration, in men and women, with a range of ages, health, cognitive and functional status. Some commonly used osmolarity equations work poorly, and should not be used. Given costs and prevalence of dehydration in older people we suggest use of the best formula by pathology laboratories using a cutpoint of 295 mOsm/L (sensitivity 85%, specificity 59%), to report dehydration risk opportunistically when serum glucose, urea and electrolytes are measured for other reasons in older adults. DRIE: Research Register for Social Care, 122273; NU-AGE: ClinicalTrials.gov NCT01754012. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Multidetector computed tomography for preoperative evaluation of vascular anatomy in living renal donors.

PubMed

Türkvatan, Aysel; Akinci, Serkan; Yildiz, Sener; Olçer, Tülay; Cumhur, Turhan

2009-04-01

Currently, multidetector computed tomographic (MDCT) angiography has become a noninvasive alternative imaging modality to catheter renal angiography for the evaluation of renal vascular anatomy in living renal donors. In this study, we investigated the diagnostic accuracy of 16-slice MDCT in the preoperative assessment of living renal donors. Fifty-nine consecutive living renal donors (32 men, 27 women) underwent MDCT angiography followed by open donor nephrectomy. All MDCT studies were performed by using a 16-slice MDCT scanner with the same protocol consisting of arterial and nephrographic phases followed by conventional abdominal radiography. The MDCT images were assessed retrospectively for the number and branching pattern of the renal arteries and for the number and presence of major or minor variants of the renal veins. The results were compared with open surgical results. The sensitivity and specificity of MDCT for the detection of anatomic variants of renal arteries including the accessory arteries (n = 9), early arterial branching (n = 7) and major renal venous anomalies including the accessory renal veins (n = 3), late venous confluence (n = 4), circumaortic (n = 2) or retroaortic (n = 3) left renal veins were 100%. However, the sensitivity for identification of minor venous variants was 79%. All of three ureteral duplications were correctly identified at excretory phase conventional abdominal radiography. Sixteen-slice MDCT is highly accurate for the identification of anatomic variants of renal arteries and veins. Dual-phase MDCT angiography including arterial and nephrographic phases followed by conventional abdominal radiography enables complete assessment of renal donors without significant increase of radiation dose. However, the evaluation of minor venous variants may be problematic because of their small diameters and poor opacification.

Comparison of computer tomographic volumetry versus nuclear split renal function to determine residual renal function after living kidney donation.

PubMed

Patankar, Khalil; Low, Ronny Su-Tong; Blakeway, Darryn; Ferrari, Paolo

2014-07-01

Living-donor kidney transplantation is an established practice. Traditionally a combination of renal scintigram and computed tomography (CT) is used to select the kidney that is to be harvested in each donor. To evaluate the ability of split renal volume (SRV) calculated from volumetric examination of CT images compared to nuclear split renal function (nSRF) derived from gamma camera scintigram to predict donor residual single kidney function after donor nephrectomy. This pilot study comprised a retrospective analysis of CT images and renal scintigrams from 12 subsequent live kidney donors who had at least 12 months post-donation renal function follow-up. nSRF derived from the renal scintigram, expressed as the right kidney's function in percent of the total, was 50.2 ± 3.3 (range, 44.1-54.0%) and SRV estimated following analysis of CT imaging was 49.0 ± 2.9 (range, 46.4-52.3%). Although the correlation between nSRF and SRV was moderate (R = 0.46), there was 92% agreement on the dominant kidney if a difference of <2% in nSRF versus SRV was considered. Post-donation glomerular filtration rate (GFR) by CKD-EPI formula was 92 ± 10 mL/min/1.73m2 at 1 year and the correlation between estimated GFR (eGFR) at 1 year and extrapolated single kidney eGFR adjusted by nSRF (R(2 )= 0.69, P = 0.0007) or SRV (R(2 )= 0.74, P = 0.0003) was similar. Calculation of SRV from pre-donation CT examination is a valid method to estimate nSRF with good concordance with nSRF determined by renal scintigram and could replace the latter in the assessment of potential kidney donors. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Influence of renal function on the association between homocysteine level and risk of ischemic stroke.

PubMed

Cheng, Yao; Kong, Fan-Zhen; Dong, Xiao-Feng; Xu, Qin-Rong; Gui, Qian; Wang, Wei; Feng, Hong-Xuan; Luo, Wei-Feng; Gao, Zong-En; Wu, Guan-Hui

2017-01-01

We examined whether the association between total homocysteine (tHCY) and risk of ischemic stroke (IS) varies depending on renal function to gain insight into why tHCY-lowering vitamins do not reduce the incidence of cardiovascular disease in clinical trials. We analyzed data from 542 IS patients with large artery atherosclerosis (LAA) or small artery occlusion (SAO) after stratification by estimated glomerular filtration rate (eGFR) to evaluate renal function. We found that tHCY level was positively associated with the occurrence of IS in both LAA (OR: 1.159, 95% CI: 1.074-1.252, P <0.001) and SAO (OR: 1.143, 95% CI: 1.064-1.228, P <0.001) patients and in LAA (OR: 1.135, 95% CI: 1.047-1.230, P =0.002) and SAO (OR: 1.159, 95% CI: 1.060-1.268, P =0.001) subgroups with normal renal function but not in LAA or SAO subgroups with renal insufficiency. eGFR level was positively associated with IS in LAA (OR: 1.022, 95% CI: 1.010-1.034, P <0.001) and SAO (OR: 1.024, 1.012-1.037, P <0.001) subgroups with normal renal function but was negatively associated with IS in LAA (OR: 0.875, 95% CI: 0.829-0.925, P <0.001) and SAO (OR: 0.890, 95% CI: 0.850-0.932, P <0.001) subgroups with renal insufficiency. Folic acid level was negatively associated with IS in LAA (OR: 0.734, 95% CI: 0.606-0.889, P =0.002) and SAO (OR: 0.861, 95% CI: 0.767-0.967, P =0.012) subgroups with renal insufficiency. Therefore, renal function as evaluated by eGFR exerts a significant influence on the association between tHCY and risk of IS.

Prospective radionuclide renal function evaluation and its correlation with radiological findings in patients with Kock pouch urinary diversion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, K.K.; Chang, L.S.; Chen, M.T.

1991-05-01

In an attempt to understand better the status of renal function after Kock pouch urinary diversion we conducted a prospective evaluation of renal function in 25 patients using the radionuclide 131iodine-hippurate. Studies were done before, and at 1 month and every 6 months for 30 months postoperatively. The radionuclide results were then compared to excretory urography and contrast study of the reservoir. Our renal function study included the determination of individual and total effective renal plasma flow (ml. per minute), the time to maximal radioactivity over the kidney (peak time in minutes) and a renogram. The mean total (both kidneys)more » effective renal plasma flow rates before (25 patients) and at month 1 (19), month 6 (14), month 12 (12), month 18 (6), month 24 (6) and month 30 (7) after operation were 385.5 +/- 112.2, 310.5 +/- 109.9, 362.7 +/- 69.2, 442.0 +/- 97.5, 468.2 +/- 82.5, 405.7 +/- 70.6 and 414.0 +/- 65.1, respectively. A comparison of individual and total effective renal plasma flow before and after operation revealed that only the change of the flow at each or both sides of the kidney before and at 1 month after the operation reached statistically significant differences, respectively (p less than 0.05, paired t test). Postoperatively 5 of 6 patients with hydronephrosis had abnormal peak time and a third segment on the renogram was performed on the corresponding side of the kidney. No reflux was noted on contrast study of the reservoir of any patient followed for up to 30 months. In conclusion, the radionuclide renal function evaluation showed a significant decrease of renal function 1 month after Kock pouch diversion, then it resumed and remained stable (neither improved nor deteriorated) for 30 months. Also the abnormal peak time and third segment on the renogram usually implicated a dilated upper urinary tract.« less

Early diagnosis of diabetic vascular complications: impairment of red blood cell deformability

NASA Astrophysics Data System (ADS)

Shin, Sehyun; Ku, Yunhee; Park, Cheol-Woo; Suh, Jang-Soo

2006-02-01

Reduced deformability of red blood cells (RBCs) may play an important role on the pathogenesis of chronic vascular complications of diabetes mellitus. However, available techniques for measuring RBC deformability often require washing process after each measurement, which is not optimal for day-to-day clinical use at point of care. The objectives of the present study are to develop a device and to delineate the correlation of impaired RBC deformability with diabetic nephropathy. We developed a disposable ektacytometry to measure RBC deformability, which adopted a laser diffraction technique and slit rheometry. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element which is in contact with the blood sample. We studied adult diabetic patients divided into three groups according to diabetic complications. Group I comprised 57 diabetic patients with normal renal function. Group II comprised 26 diabetic patients with chronic renal failure (CRF). Group III consisted of 30 diabetic subjects with end-stage renal disease (ESRD) on hemodialysis. According to the renal function for the diabetic groups, matched non-diabetic groups were served as control. We found substantially impaired red blood cell deformability in those with normal renal function (group I) compared to non-diabetic control (P = 0.0005). As renal function decreases, an increased impairment in RBC deformability was found. Diabetic patients with chronic renal failure (group II) when compared to non-diabetic controls (CRF) had an apparently greater impairment in RBC deformability (P = 0.07). The non-diabetic cohort (CRF), on the other hand, manifested significant impairment in red blood cell deformability compared to healthy control (P = 0.0001). The newly developed slit ektacytometer can measure the RBC deformability with ease and accuracy. In addition, progressive impairment in cell deformability is associated with renal function loss in all patients regardless of the presence or absence of diabetes. In diabetic patients, early impairment in RBC deformability appears in patients with normal renal function.

Diabetic nephropathy: a strong predictor of sleep quality in hemodialysis patients.

PubMed

Edalat-Nejad, Mahnaz; Jafarian, Nahid; Yousefichaijan, Parsa

2014-07-01

Sleep complaints are common in hemodialysis (HD) patients. Sleep quality (SQ) is a predictor of quality of life and mortality risk in HD. The aim of this study was to examine factors that may have a role in SQ. In this cross-sectional analytic study, 138 end-stage renal disease patients receiving maintenance HD for >3 months were included. The Pittsburgh Sleep Quality Index (PSQI) was used to measure individual's SQ. Patients with a global PSQI score >5 were assumed as poor sleepers. Eighty-eight patients (64%) were classified as poor sleepers. Poor sleepers were older and more likely had diabetes. They had significantly higher serum ferritin and calcium levels and lower serum parathyroid hormone level (all P-values <0.05). The global PSQI score was positively correlated with age, serum calcium level and presence of diabetes as the underlying cause of renal failure. In the multi-variable binary regression model, presence of diabetes (Odds Ratio (OR) = 3.67, P = 0.008) and body pain (OR = 1.182, P = 0.014) were the significant independent predictors for poor SQ. Poor SQ was common among our HD patients, especially among diabetic cases and, therefore, there is a need to pay more attention to the care of this subgroup with regard to the diagnosis and management of sleep complaints.

Functional significance of the pattern of renal sympathetic nerve activation.

PubMed

Dibona, G F; Sawin, L L

1999-08-01

To assess the renal functional significance of the pattern of renal sympathetic nerve activation, computer-generated stimulus patterns (delivered at constant integrated voltage) were applied to the decentralized renal sympathetic nerve bundle and renal hemodynamic and excretory responses determined in anesthetized rats. When delivered at the same integrated voltage, stimulus patterns resembling those observed in in vivo multifiber recordings of renal sympathetic nerve activity (diamond-wave patterns) produced greater renal vasoconstrictor responses than conventional square-wave patterns. Within diamond-wave patterns, increasing integrated voltage by increasing amplitude produced twofold greater renal vasoconstrictor responses than by increasing duration. With similar integrated voltages that were subthreshold for renal vasoconstriction, neither diamond- nor square-wave pattern altered glomerular filtration rate, whereas diamond- but not square-wave pattern reversibly decreased urinary sodium excretion by 25 +/- 3%. At the same number of pulses per second, intermittent stimulation produced faster and greater renal vasoconstriction than continuous stimulation. At the same number of pulses per second, increases in rest period during intermittent stimulation proportionally augmented the renal vasoconstrictor response compared with that observed with continuous stimulation; the maximum augmentation of 55% occurred at a rest period of 500 ms. These results indicate that the pattern of renal sympathetic nerve stimulation (activity) significantly influences the rapidity, magnitude, and selectivity of the renal vascular and tubular responses.

The Clinical Spectrum of Renal Insufficiency During Acute Glomerulonephritis in the Adult

PubMed Central

Lemieux, Guy; Cuvelier, Amedee A.; Lefebvre, Rene

1967-01-01

Twenty-seven adults with acute poststreptococcal glomerulonephritis were divided into two groups according to the severity of reduction in renal function: (1) 14 patients with mild depression of renal function, and (2) 13 patients with more severe renal insufficiency. In the first group the outcome was favourable, with complete clinical recovery in 11 patients. Only two patients in the second group have recovered. Five have died of renal failure and in six the chronic stage has developed. The most notable histopathological lesion observed in this group of patients was severe proliferative glomerulonephritis with a large number of epithelial crescents. According to the mode of development and time of onset of renal failure, these 13 patients could be divided into three sub-groups: (1) early renal failure without oliguria (three patients), (2) early renal failure with severe oliguria or anuria (three patients) and (3) delayed renal failure (seven patients). Although there are exceptions, the development of renal insufficiency in an adult patient suffering from acute glomerulonephritis is usually associated with a guarded prognosis. ImagesFig. 2 PMID:6021561

Three new renal simulators for use in nuclear medicine

NASA Astrophysics Data System (ADS)

Dullius, Marcos; Fonseca, Mateus; Botelho, Marcelo; Cunha, Clêdison; Souza, Divanízia

2014-03-01

Renal scintigraphy is useful to provide both functional and anatomic information of renal flow of cortical functions and evaluation of pathological collecting system. The objective of this study was develop and evaluate the performance of three renal phantoms: Two anthropomorphic static and another dynamic. The static images of the anthropomorphic phantoms were used for comparison with static renal scintigraphy with 99mTc-DMSA in different concentrations. These static phantoms were manufactured in two ways: one was made of acrylic using as mold a human kidney preserved in formaldehyde and the second was built with ABS (acrylonitrile butadiene styrene) in a 3D printer. The dynamic renal phantom was constructed of acrylic to simulate renal dynamics in scintigraphy with 99mTc-DTPA. These phantoms were scanned with static and dynamic protocols and compared with clinical data. Using these phantoms it is possible to acquire similar renal images as in the clinical scintigraphy. Therefore, these new renal phantoms can be very effective for use in the quality control of renal scintigraphy, and image processing systems.

Delafloxacin Pharmacokinetics in Subjects With Varying Degrees of Renal Function.

PubMed

Hoover, Randall K; Alcorn, Harry; Lawrence, Laura; Paulson, Susan K; Quintas, Megan; Cammarata, Sue K

2018-04-01

Delafloxacin, a fluoroquinolone, has activity against gram-positive organisms including methicillin-resistant Staphylococcus aureus and fluoroquinolone-susceptible and -resistant gram-negative organisms. This study was conducted to determine delafloxacin pharmacokinetics after a single intravenous infusion or oral dose administration in subjects with varying degrees of renal function. The study was an open-label, parallel-group crossover study in subjects with normal renal function or with mild, moderate, or severe renal impairment. Subjects received 300 mg delafloxacin intravenously, placebo intravenously, and 400 mg delafloxacin orally in 3 periods separated by ≥14-day washouts. Blood and urine pharmacokinetic parameters were calculated using noncompartmental methods. Delafloxacin total clearance decreased with decreasing renal function, with a corresponding increase in AUC 0-∞ . After intravenous administration, mean total clearance was 13.7 and 7.07 L/h, and mean AUC 0-∞ was 22.6 and 45.0 μg·h/mL in normal and severe renal subjects, respectively. Mean renal clearance as determined by urinary excretion was 6.03 and 0.44 L/h in normal and severe renal impairment subjects, respectively. Total clearance exhibited linear relationships to eGFR and CL CR . Similar observations were found after oral administration of delafloxacin. Single doses of delafloxacin 300 mg intravenously and 400 mg orally were well tolerated in all groups. In conclusion, renal insufficiency has an effect on delafloxacin clearance; a dosing adjustment for intravenous dosing is warranted for patients with severe renal impairment (eGFR < 30 mL/min). © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Longitudinal development of renal damage and renal function in infants with high grade vesicoureteral reflux.

PubMed

Sjöström, Sofia; Jodal, Ulf; Sixt, Rune; Bachelard, Marc; Sillén, Ulla

2009-05-01

We sought to study renal abnormality and renal function through time in infants with high grade vesicoureteral reflux. This prospective observational study included 115 infants (80 boys and 35 girls) younger than 1 year with grade III to V vesicoureteral reflux. The diagnosis was made after prenatal ultrasound in 26% of the patients and after urinary tract infection in 71%. Patients were followed by renal scintigraphy, 51chromium edetic acid clearance and video cystometry. Median followup was 62 months. Renal abnormality, which was found in 90% of the children at followup, was generalized in 71% and focal in 29%. The abnormality was bilateral in 28% of the affected patients. Total glomerular filtration rate was less than 80% of expected in 30% of the patients. Single kidney function was less than 40% of expected total glomerular filtration rate in 71% of the patients. Renal status (parenchymal abnormality and function) remained unchanged through time in 84 of 108 available cases (78%), improved in 5 (5%) and deteriorated in 19 (18%). Predictive factors for deterioration were recurrent febrile urinary tract infection, bilateral abnormality and reduced total glomerular filtration rate. Deteriorated renal status was more common in cases diagnosed prenatally than in those detected after urinary tract infection. Among these infants with high grade vesicoureteral reflux renal abnormality was frequent and was associated with subnormal filtration of one of the kidneys. Decreased total glomerular filtration rate was seen in about a third of the patients. Overall deterioration of renal status was seen in only a fifth of the patients. Infection control seems to be an important factor to minimize the risk.

P wave dispersion and maximum P wave duration are independently associated with rapid renal function decline.

PubMed

Su, Ho-Ming; Tsai, Wei-Chung; Lin, Tsung-Hsien; Hsu, Po-Chao; Lee, Wen-Hsien; Lin, Ming-Yen; Chen, Szu-Chia; Lee, Chee-Siong; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung

2012-01-01

The P wave parameters measured by 12-lead electrocardiogram (ECG) are commonly used as noninvasive tools to assess for left atrial enlargement. There are limited studies to evaluate whether P wave parameters are independently associated with decline in renal function. Accordingly, the aim of this study is to assess whether P wave parameters are independently associated with progression to renal end point of ≥25% decline in estimated glomerular filtration rate (eGFR). This longitudinal study included 166 patients. The renal end point was defined as ≥25% decline in eGFR. We measured two ECG P wave parameters corrected by heart rate, i.e. corrected P wave dispersion (PWdisperC) and corrected P wave maximum duration (PWdurMaxC). Heart function and structure were measured from echocardiography. Clinical data, P wave parameters, and echocardiographic measurements were compared and analyzed. Forty-three patients (25.9%) reached renal end point. Kaplan-Meier curves for renal end point-free survival showed PWdisperC > median (63.0 ms) (log-rank P = 0.004) and PWdurMaxC > median (117.9 ms) (log-rank P<0.001) were associated with progression to renal end point. Multivariate forward Cox-regression analysis identified increased PWdisperC (hazard ratio [HR], 1.024; P = 0.001) and PWdurMaxC (HR, 1.029; P = 0.001) were independently associated with progression to renal end point. Our results demonstrate that increased PWdisperC and PWdurMaxC were independently associated with progression to renal end point. Screening patients by means of PWdisperC and PWdurMaxC on 12 lead ECG may help identify a high risk group of rapid renal function decline.

Robot-assisted laparoscopic partial nephrectomy versus laparoscopic partial nephrectomy: A propensity score-matched comparative analysis of surgical outcomes and preserved renal parenchymal volume.

PubMed

Tachibana, Hidekazu; Takagi, Toshio; Kondo, Tsunenori; Ishida, Hideki; Tanabe, Kazunari

2018-04-01

To compare surgical outcomes, including renal function and the preserved renal parenchymal volume, between robot-assisted laparoscopic partial nephrectomy and laparoscopic partial nephrectomy using propensity score-matched analyses. In total, 253 patients, with a normal contralateral kidney, who underwent laparoscopic partial nephrectomy (n = 131) or robot-assisted laparoscopic partial nephrectomy (n = 122) with renal arterial clamping between 2010 and 2015, were included. Patients' background and tumor factors were adjusted by propensity score matching. Surgical outcomes, including postoperative renal function, complications, warm ischemia time and preserved renal parenchymal volume, evaluated by volumetric analysis, were compared between the surgical procedures. After matching, 64 patients were assigned to each group. The mean age was 56-57 years, and the mean tumor size was 22 mm. Approximately 50% of patients had low complexity tumors (RENAL nephrometry score 4-7). The incidence rate of acute kidney failure was significantly lower in the robot-assisted laparoscopic partial nephrectomy (11%) than laparoscopic partial nephrectomy (23%) group (P = 0.049), and warm ischemia time shorter in the robot-assisted laparoscopic partial nephrectomy (17 min) than laparoscopic partial nephrectomy (25 min) group (P < 0.0001). The preservation rate of renal function, measured by the estimated glomerular filtration rate, at 6 months post-surgery was 96% for robot-assisted laparoscopic partial nephrectomy and 90% for laparoscopic partial nephrectomy (P < 0.0001). The preserved renal parenchymal volume was higher for robot-assisted laparoscopic partial nephrectomy (89%) than laparoscopic partial nephrectomy (77%; P < 0.0001). The rate of perioperative complications, surgical margin status and length of hospital stay were equivalent for both techniques. Robot-assisted laparoscopic partial nephrectomy allows to achieve better preservation of renal function and parenchymal volume than laparoscopic partial nephrectomy. © 2018 The Japanese Urological Association.

Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

PubMed

Coutinho, João V S; Freitas-Lima, Leandro C; Freitas, Frederico F C T; Freitas, Flávia P S; Podratz, Priscila L; Magnago, Rafaella P L; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Brandão, Poliane A A; Carneiro, Maria T W D; Paiva-Melo, Francisca D; Miranda-Alves, Leandro; Silva, Ian V; Gava, Agata L; Graceli, Jones B

2016-10-17

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Primary Renal Rhabdomyosarcoma in an Adolescent With Tumor Thrombosis in the Inferior Vena Cava and Right Atrium: A Case Report and Review of the Literature.

PubMed

Lin, Wei-Ching; Chen, Jeon-Hor; Westphalen, Antonio; Chang, Han; Chiang, I-Ping; Chen, Cheng-Hong; Wu, Hsi-Chin; Lin, Chien-Heng

2016-05-01

Although the second peak of the age distribution of rhabdomyosarcoma (RMS) is at adolescence, renal RMS is extremely rare at this age group. This tumor is indistinguishable from other renal tumors based on clinical and imaging findings, and the diagnosis relies on histology and immunohistochemical staining. We report a unique case of adolescent renal RMS associated with tumor thrombus extending into the inferior vena cava (IVC) and right atrium.An 18-year-old female adolescent presented with shortness of breath and palpitations, associated with right flank discomfort, and hematuria. A pleomorphic-type renal RMS with Budd-Chiari syndrome and arrhythmia induced by IVC and RA thrombosis was diagnosed. Despite complete tumor resection, the patient developed multiple lung metastases a month after surgery. Chemotherapy was recommended, but the patient declined. She died within a year of the initial operation.Adolescent renal RMS is rare and associated with poor outcome. Early aggressive multimodal therapy seems to be appropriate, in particular, in the presence of tumor thrombosis.

Oral Manifestations in a Renal Osteodystrophy Patient - A Case Report with Review of Literature

PubMed Central

Nisha V, Aarthi; GS, Asokan; CA, Prakash; MM, Varadharaja

2014-01-01

Renal Osteodystrophy (ROD) is a common complication of chronic renal disease (CRD) and is the part of a broad spectrum of disorders of mineral metabolism that occurs in the clinical setting. It occurs early in the course of chronic renal failure and progresses as the kidney function deteriorates. It is an osseous alteration believed to arise from increased parathyroid function associated with inappropriate calcium, phosphorus and vitamin D metabolism. Involvement of the jaws is common and radiographic alterations are often one of the earliest signs of chronic renal failure. Herein, reporting a case of Chronic Renal Failure (Bilateral Grade I Neuropathy) with ROD presenting oral manifestations in an 11-year -old male child. PMID:25302278

Dissecting the roles of aquaporins in renal pathophysiology using transgenic mice

PubMed Central

Verkman, A. S.

2008-01-01

Transgenic mice lacking renal aquaporins (AQPs), or containing mutated AQPs, have been useful in confirming anticipated AQP functions in renal physiology and in discovering new functions. Mice lacking AQPs 1–4 manifest defects in urinary concentrating ability to different extents. Mechanistic studies have confirmed the involvement of AQP1 in near-isosmolar fluid absorption in proximal tubule, and in countercurrent multiplication and exchange mechanisms that produce medullary hypertonicity in the antidiuretic kidney. Deletion of AQPs 2–4 impairs urinary concentrating ability by reduction of transcellular water permeability in collecting duct. Recently created transgenic mouse models of nephrogenic diabetes insipidus produced by AQP2 gene mutation offer exciting possibilities to test new drug therapies. Several unanticipated AQP functions in kidney have been discovered recently that are unrelated to their role in transcellular water transport. There is evidence for involvement of AQP1 in kidney cell migration following renal injury, of AQP7 in renal glycerol clearance, of AQP11 in prevention of renal cystic disease, and possibly of AQP3 in regulation of collecting duct cell proliferation. Future work in renal AQPs will focus on mechanisms responsible for these non-fluid-transporting functions, and on the development of small-molecule AQP inhibitors for use as aquaretic-type diuretics. PMID:18519083

Assessment of myocardial mechanics in patients with end-stage renal disease and renal transplant recipients using speckle tracking echocardiography.

PubMed

Pirat, Bahar; Bozbas, Huseyin; Simsek, Vahide; Sade, L Elif; Sayin, Burak; Muderrisoglu, Haldun; Haberal, Mehmet

2015-04-01

Velocity vector imaging allows quantitation of myocardial strain and strain rate from 2-dimensional images based on speckle tracking echocardiography. The aim of this study was to analyze the changes in myocardial strain and strain rate patterns in patients with end-stage renal disease and renal transplant recipients. We studied 33 patients with end-stage renal disease on hemodialysis (19 men; mean age, 36 ± 8 y), 24 renal transplant recipients with functional grafts (21 men; mean age, 36 ± 7 y) and 26 age- and sex-matched control subjects. Longitudinal peak systolic strain and strain rate for basal, mid, and apical segments of the left ventricular wall were determined by velocity vector imaging from apical 4- and 2-chamber views. The average longitudinal strain and strain rate for the left ventricle were noted. From short-axis views at the level of papillary muscles, average circumferential, and radial strain, and strain rate were assessed. Mean heart rate and systolic and diastolic blood pressure during imaging were similar between the groups. Longitudinal peak systolic strain and strain rate at basal and mid-segments of the lateral wall were significantly higher in renal transplant recipients and control groups than endstage renal disease patients. Average longitudinal systolic strain from the 4-chamber view was highest in control subjects (-14.5% ± 2.9%) and was higher in renal transplant recipients (-12.5% ± 3.0%) than end-stage renal disease patients (-10.2% ± 1.6%; P ≤ .001). Radial and circumferential strain and strain rate at the level of the papillary muscle were lower in patients with end-stage renal disease than other groups. Differences in myocardial function in patients with end-stage renal disease, renal transplant recipients, and normal controls can be quantified by strain imaging. Myocardial function is improved in renal transplant recipients compared with end-stage renal disease patients.

The association between elevated serum uric acid level and an increased risk of renal function decline in a health checkup cohort in China.

PubMed

Cao, Xia; Wu, Liuxin; Chen, Zhiheng

2018-03-01

To investigate whether an elevated serum uric acid (SUA) level is an independent risk factor for rapid decline in renal function or new-onset chronic kidney disease (CKD) in a Chinese health checkup population. A cohort study of 6495 Chinese individuals who underwent health checkups with normal estimated glomerular filtration rate (eGFR) at baseline was carried out from May 2011 to April 2016. Examinations included a questionnaire, physical measurements, and blood sampling. The gender-specific quartiles of blood uric acid were used to present baseline descriptive data. Rapid decline of renal function was defined as eGFR loss of > 3 mL/min/1.73 m 2 /year. New-onset CKD was defined as follow-up eGFR < 60 mL/min/1.73 m 2 or positive proteinuria. Multivariable logistic regression was used to assess the relationship between serum uric acid and the following outcomes: rapid decline of renal function, incident CKD, and combined renal outcomes. During mean follow-up of 52.8 months, 1608 (24.8%) individuals reached combined renal events. Rapid decline in renal function developed in 1506 (23.2%) individuals, and incident CKD was documented in 372 (5.7%) individuals. In a multivariate model adjusted for age, BMI, diabetes, hypertension, alcohol drinking, SBP, total cholesterol, and eGFR, the odds ratio for rapid decline of renal function increased across quartiles of serum uric acid level, reaching a 1.32 (95% CI 1.02-2.97) for the top quartile compared to the lowest quartile (P for trend < 0.001). Meanwhile, higher SUA was also associated with incident CKD in all models. Furthermore, an increased risk of reaching renal outcomes across increasing quartiles of SUA levels appeared to be similar among subgroups stratified according to age, eGFR, and SBP (P < 0.05 in all). These findings suggest that higher SUA may predict progressive renal damage and dysfunction in a health checkup population in China.

Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

PubMed

Miyamoto, Koji; Aiba, Takeshi; Arihiro, Shoji; Watanabe, Makoto; Kokubo, Yoshihiro; Ishibashi, Kohei; Hirose, Sayako; Wada, Mitsuru; Nakajima, Ikutaro; Okamura, Hideo; Noda, Takashi; Nagatsuka, Kazuyuki; Noguchi, Teruo; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kamakura, Shiro; Shimizu, Wataru; Miyamoto, Yoshihiro; Toyoda, Kazunori; Kusano, Kengo

2016-08-01

Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) ≥ 50 ml/min (mean age 68 ± 11 years, mean CHADS2 score = 1.8 ± 1.4, CHA2DS2-VASc score = 2.8 ± 1.8, HAS-BLED score = 1.7 ± 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr ≥ 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 ± 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr ≥ 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and ≥3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1-2, 3-4 and ≥5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr ≥ 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was not uncommon and was associated with more frequent adverse events including major bleeding in NVAF patients with anticoagulation therapy. CHADS2, CHA2DS2-VASc, and HAS-BLED scores may be useful as an index of predicting renal function deterioration.

Plasma Proenkephalin and Poor Long-Term Outcome in Renal Transplant Recipients

PubMed Central

Kieneker, Lyanne M.; Hartmann, Oliver; Struck, Joachim; Bergmann, Andreas; Gansevoort, Ron T.; Joosten, Michel M.; van den Berg, Else; de Boer, Rudolf A.; Bakker, Stephan J.L.

2017-01-01

Background Proenkephalin (pro-ENK), a stable and reliable surrogate marker for unstable enkephalins, was found to be associated with acute kidney injury and chronic renal failure in previous studies. We aimed to investigate whether pro-ENK is linked to chronic kidney injury and poor long-term outcome in renal transplant recipients (RTR). Methods We included 664 stable RTR and 95 healthy kidney donors. Pro-ENK was measured in plasma with a double monoclonal sandwich immunoassay. Graft failure was defined as return to dialysis therapy or retransplantation. Results Median pro-ENK was 110 pmol/L (interquartile range [IQR], 85-148 pmol/L) in RTR and 48 pmol/L (IQR, 42-55 pmol/L) in kidney donors. Pro-ENK was correlated with estimated glomerular filtration rate (GFR) (rs = −0.80, P < 0.001) in RTR and with measured GFR (rs = −0.74, P < 0.001) in kidney donors. During a median follow-up of 3.1 years (IQR, 2.7-3.9 years), 45 RTR developed graft failure and 76 died. Pro-ENK was positively associated with risk (hazard ratio [HR] per standard deviation increment of the logarithm of pro-ENK; 95% confidence interval [CI]) of graft failure (HR, 4.80; 95% CI, 3.55-6.48) and mortality (HR, 1.50; 95% CI, 1.22-1.85). After adjustment of age, sex, and estimated GFR, the association of pro-ENK with graft failure remained significant (HR, 2.36; 95% CI, 1.37-4.06), whereas no significant association of pro-ENK with risk of all-cause mortality was observed (HR, 1.34; 95% CI, 0.90-2.09). Conclusions Plasma pro-ENK is associated with kidney function as reflected by correlations with measured GFR in both RTR and kidney donors. In addition, pro-ENK was independently associated with increased risk of graft failure in RTR. Pro-ENK may aid in identification of RTR at risk for late graft failure. PMID:28795142

Variation of renal function over time is associated with major bleeding in patients treated with direct oral anticoagulants for atrial fibrillation.

PubMed

Becattini, C; Giustozzi, M; Ranalli, M G; Bogliari, G; Cianella, F; Verso, M; Agnelli, G; Vedovati, M C

2018-05-01

Essential In patients on treatment with direct anticoagulants (DOACs) variation of renal function is common. The effect of variations of renal function over time on major bleeding is not well defined. Variation of renal function over time is an independent predictor of major bleeding. Identifying conditions associated with variation of renal function may increase safety of DOACs. Background Chronic kidney disease is a risk factor for major bleeding in patients with atrial fibrillation (AF) treated with warfarin. Objective To assess the effect of variations in renal function over time on the risk of major bleeding during treatment with direct oral anticoagulants (DOACs) in patients with non-valvular AF. Methods Consecutive AF patients were prospectively followed after they had received the first DOAC prescription. Estimated glomerular filtration rate (eGFR) was periodically assessed, and the incidence of major bleeding was recorded. A joint survival model was used to estimate the association between variation in eGFR and the risk of major bleeding. Results During a mean follow-up of 575 days, 44 major bleeds occurred in 449 patients (6.1% per patient-year). eGFR over time was inversely and independently associated with the risk of major bleeding; every 1 mL min -1 absolute decrease in eGFR was associated with a 2% increase in the risk of major bleeding (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.04). A similar effect of the variation in eGFR over time was observed on the risk of clinically relevant non-major bleeding (HR 1.02, 95% CI 1.01-1.03). Deterioration of renal function leading to a change in eGFR staging was associated with an increase in the risk of major bleeding (HR 2.43, 95% CI 1.33-4.45). Conclusions Variation in renal function over time is associated with the risk of major bleeding in AF patients treated with DOACs in real life. Identification of intervening clinical conditions associated with variation in renal function is essential to reduce the risk of major bleeding and to make DOAC treatment more safe. © 2018 International Society on Thrombosis and Haemostasis.

Effect of whole soy and purified isoflavone daidzein on renal function--a 6-month randomized controlled trial in equol-producing postmenopausal women with prehypertension.

PubMed

Liu, Zhao-min; Ho, Suzanne C; Chen, Yu-ming; Tang, Nelson; Woo, Jean

2014-09-01

The aim of the study was to examine the long-term effect of commonly used whole soy foods (soy flour) and purified daidzein (one major isoflavone and the precursor of equol) on renal function among prehypertensive postmenopausal women who are also equol producers, a population most likely to benefit from soy intervention. This was a 6-month double-blind, randomized, placebo-controlled trial. Two hundred seventy eligible Chinese women were randomized to either one of the three treatments: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo group) daily each for 6 months. Fasting blood and 24-h urine samples were collected at the beginning and end of trial. Serum creatinine, cystatin C, urea, angiotensin-converting enzyme, minerals and 24-h urinary creatinine and minerals were analyzed. Estimated glomerular filtration rate (eGFR) was calculated with the Cockcroft-Gault and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Two hundred fifty-three subjects completed the study according to the protocol. Urinary isoflavones indicated good compliance of participants. No significant changes were observed in most of renal parameters, however, there was a less decrease in eGFRcockcroft in 6-month change (p=0.044) and %change (p=0.031) with whole soy intake relative to milk placebo. Subgroup analysis among women with lowered renal function suggested whole soy consumption tended to improve markers of renal function relative to control. Six-month consumption of whole soy tended to have a modest improvement of renal function in prehypertensive postmenopausal women with lowered renal function. Future trials in subjects with more declined renal function are necessary. The trial was registered in ClinicalTrials.gov with identifier of NCT01270737. (URL: http://clinicaltrials.gov/ct2/show/NCT01270737). Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.